@article{kim_schulte_sarver_lee_angelos_frantz_forster_timothy d. o'brien_cornax_o'sullivan_et al._2024, title={Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion}, volume={4}, ISSN={["2767-9764"]}, DOI={10.1158/2767-9764.CRC-23-0441}, abstractNote={Abstract Hemangiosarcoma and angiosarcoma are soft-tissue sarcomas of blood vessel–forming cells in dogs and humans, respectively. These vasoformative sarcomas are aggressive and highly metastatic, with disorganized, irregular blood-filled vascular spaces. Our objective was to define molecular programs which support the niche that enables progression of canine hemangiosarcoma and human angiosarcoma. Dog-in-mouse hemangiosarcoma xenografts recapitulated the vasoformative and highly angiogenic morphology and molecular characteristics of primary tumors. Blood vessels in the tumors were complex and disorganized, and they were lined by both donor and host cells. In a series of xenografts, we observed that the transplanted hemangiosarcoma cells created exuberant myeloid hyperplasia and gave rise to lymphoproliferative tumors of mouse origin. Our functional analyses indicate that hemangiosarcoma cells generate a microenvironment that supports expansion and differentiation of hematopoietic progenitor populations. Furthermore, gene expression profiling data revealed hemangiosarcoma cells expressed a repertoire of hematopoietic cytokines capable of regulating the surrounding stromal cells. We conclude that canine hemangiosarcomas, and possibly human angiosarcomas, maintain molecular properties that provide hematopoietic support and facilitate stromal reactions, suggesting their potential involvement in promoting the growth of hematopoietic tumors. Significance: We demonstrate that hemangiosarcomas regulate molecular programs supporting hematopoietic expansion and differentiation, providing insights into their potential roles in creating a permissive stromal-immune environment for tumor progression.}, number={6}, journal={CANCER RESEARCH COMMUNICATIONS}, author={Kim, Jong Hyuk and Schulte, Ashley J. and Sarver, Aaron L. and Lee, Donghee and Angelos, Mathew G. and Frantz, Aric M. and Forster, Colleen L. and Timothy D. O'Brien and Cornax, Ingrid and O'Sullivan, M. Gerard and et al.}, year={2024}, month={Jun}, pages={1467–1480} }
 @article{scheible_stinson_breen_callahan_thomas_meiklejohn_2024, title={The development of non-destructive sampling methods of parchment skins for genetic species identification}, volume={19}, ISSN={["1932-6203"]}, url={https://doi.org/10.1371/journal.pone.0299524}, DOI={10.1371/journal.pone.0299524}, abstractNote={Parchment, the skins of animals prepared for use as writing surfaces, offers a valuable source of genetic information. Many have clearly defined provenance, allowing for the genetic findings to be evaluated in temporal and spatial context. While these documents can yield evidence of the animal sources, the DNA contained within these aged skins is often damaged and fragmented. Previously, genetic studies targeting parchment have used destructive sampling techniques and so the development and validation of non-destructive sampling methods would expand opportunities and facilitate testing of more precious documents, especially those with historical significance. Here we present genetic data obtained by non-destructive sampling of eight parchments spanning the 15th century to the modern day. We define a workflow for enriching the mitochondrial genome (mtGenome), generating next-generation sequencing reads to permit species identification, and providing interpretation guidance. Using sample replication, comparisons to destructively sampled controls, and by establishing authentication criteria, we were able to confidently assign full/near full mtGenome sequences to 56.3% of non-destructively sampled parchments, each with greater than 90% of the mtGenome reference covered. Six of eight parchments passed all four established thresholds with at least one non-destructive sample, highlighting promise for future studies.}, number={3}, journal={PLOS ONE}, author={Scheible, Melissa and Stinson, Timothy L. and Breen, Matthew and Callahan, Benjamin J. and Thomas, Rachael and Meiklejohn, Kelly A.}, editor={Shakoori, Abdul RaufEditor}, year={2024}, month={Mar} }
 @article{bray_eward_breen_2023, title={Defining the relevance of surgical margins. Part two: Strategies to improve prediction of recurrence risk}, ISSN={["1476-5829"]}, DOI={10.1111/vco.12881}, abstractNote={Abstract}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Bray, Jonathan and Eward, Will and Breen, Matthew}, year={2023}, month={Feb} }
 @article{gregory_livingston_hawkins_loyola_cave_vaden_deresienski_breen_riofrio-lazo_lewbart_et al._2023, title={Dirofilaria immitis Identified in Galapagos Sea Lions (Zalophus wollebaeki): A Wildlife Health and Conservation Concern}, volume={59}, ISSN={["1943-3700"]}, DOI={10.7589/JWD-D-22-00119}, abstractNote={Abstract: The Galapagos sea lion (Zalophus wollebaeki), an endemic and endangered pinniped, faces an increasing threat due to infectious diseases related to domestic animals. Dirofilaria immitis, the parasite responsible for canine heartworm disease, is one such threat, as canine infections on the archipelago have been documented. We used a canine heartworm antigen test kit to analyze the blood from 25 juvenile Galapagos sea lions for D. immitis. Two (8%) sea lions tested positive for D. immitis antigen. Using morphologic and genetic assessments, we evaluated 20 filarial-like worms collected from within the heart of an adult male Galapagos sea lion during a previous routine postmortem examination. The intracardiac worms were morphologically consistent with adult D. immitis, and sequence analysis of targeted PCR amplicons confirmed their identity. This is the first report of D. immitis infection in Galapagos sea lions, which could become a major health problem for these pinnipeds. Further studies are necessary to confirm the level of threat from this parasite; however, widespread adoption of routine heartworm testing, prevention, and treatment in the canine population, and the control of mosquitos, could potentially reduce the disease impact on this endangered pinniped species.}, number={3}, journal={JOURNAL OF WILDLIFE DISEASES}, author={Gregory, Taylor M. and Livingston, Isabella and Hawkins, Eleanor C. and Loyola, Andrea and Cave, Ashley and Vaden, Shelly L. and Deresienski, Diane and Breen, Matthew and Riofrio-Lazo, Marjorie and Lewbart, Gregory A. and et al.}, year={2023}, month={Jul}, pages={487–494} }
 @article{spatola_buckley_dillon_v. dutrow_betz_pilot_parker_bogdanowicz_thomas_chyzhevskyi_et al._2023, title={The dogs of Chernobyl: Demographic insights into populations inhabiting the nuclear exclusion zone}, volume={9}, ISSN={["2375-2548"]}, DOI={10.1126/sciadv.ade2537}, abstractNote={The 1986 Chernobyl nuclear disaster initiated a series of catastrophic events resulting in long-term and widespread environmental contamination. We characterize the genetic structure of 302 dogs representing three free-roaming dog populations living within the power plant itself, as well as those 15 to 45 kilometers from the disaster site. Genome-wide profiles from Chernobyl, purebred and free-breeding dogs, worldwide reveal that the individuals from the power plant and Chernobyl City are genetically distinct, with the former displaying increased intrapopulation genetic similarity and differentiation. Analysis of shared ancestral genome segments highlights differences in the extent and timing of western breed introgression. Kinship analysis reveals 15 families, with the largest spanning all collection sites within the radioactive exclusion zone, reflecting migration of dogs between the power plant and Chernobyl City. This study presents the first characterization of a domestic species in Chernobyl, establishing their importance for genetic studies into the effects of exposure to long-term, low-dose ionizing radiation.}, number={9}, journal={SCIENCE ADVANCES}, author={Spatola, Gabriella J. and Buckley, Reuben M. and Dillon, Megan and V. Dutrow, Emily and Betz, Jennifer A. and Pilot, Malgorzata and Parker, Heidi G. and Bogdanowicz, Wieslaw and Thomas, Rachel and Chyzhevskyi, Ihor and et al.}, year={2023}, month={Mar} }
 @article{thomas_wiley_droste_robertson_inman_breen_2023, title={Whole exome sequencing analysis of canine urothelial carcinomas without BRAF V595E mutation: Short in-frame deletions in BRAF and MAP2K1 suggest alternative mechanisms for MAPK pathway disruption}, volume={19}, ISSN={["1553-7404"]}, url={https://doi.org/10.1371/journal.pgen.1010575}, DOI={10.1371/journal.pgen.1010575}, abstractNote={Molecular profiling studies have shown that 85% of canine urothelial carcinomas (UC) harbor an activating BRAF V595E mutation, which is orthologous to the V600E variant found in several human cancer subtypes. In dogs, this mutation provides both a powerful diagnostic marker and a potential therapeutic target; however, due to their relative infrequency, the remaining 15% of cases remain understudied at the molecular level. We performed whole exome sequencing analysis of 28 canine urine sediments exhibiting the characteristic DNA copy number signatures of canine UC, in which the BRAF V595E mutation was undetected (UDV595E specimens). Among these we identified 13 specimens (46%) harboring short in-frame deletions within either BRAF exon 12 (7/28 cases) or MAP2K1 exons 2 or 3 (6/28 cases). Orthologous variants occur in several human cancer subtypes and confer structural changes to the protein product that are predictive of response to different classes of small molecule MAPK pathway inhibitors. DNA damage response and repair genes, and chromatin modifiers were also recurrently mutated in UDV595E specimens, as were genes that are positive predictors of immunotherapy response in human cancers. Our findings suggest that short in-frame deletions within BRAF exon 12 and MAP2K1 exons 2 and 3 in UDV595E cases are alternative MAPK-pathway activating events that may have significant therapeutic implications for selecting first-line treatment for canine UC. We developed a simple, cost-effective capillary electrophoresis genotyping assay for detection of these deletions in parallel with the BRAF V595E mutation. The identification of these deletion events in dogs offers a compelling cross-species platform in which to study the relationship between somatic alteration, protein conformation, and therapeutic sensitivity.}, number={4}, journal={PLOS GENETICS}, author={Thomas, Rachael and Wiley, Claire A. and Droste, Emma L. and Robertson, James and Inman, Brant A. and Breen, Matthew}, editor={Leeb, TossoEditor}, year={2023}, month={Apr} }
 @article{bray_eward_breen_2022, title={Evaluating the relevance of surgical margins. Part one: The problems with current methodology}, ISSN={["1476-5829"]}, DOI={10.1111/vco.12865}, abstractNote={Abstract}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Bray, Jonathan and Eward, Will and Breen, Matthew}, year={2022}, month={Nov} }
 @article{krane_shockley_malarkey_miller_miller_tokarz_jensen_janardhan_breen_mariani_2022, title={Inter-pathologist agreement on diagnosis, classification and grading of canine glioma}, volume={7}, ISSN={["1476-5829"]}, url={https://doi.org/10.1111/vco.12853}, DOI={10.1111/vco.12853}, abstractNote={Abstract}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Krane, Gregory A. and Shockley, Keith R. and Malarkey, David E. and Miller, Andrew D. and Miller, C. Ryan and Tokarz, Debra A. and Jensen, Heather L. and Janardhan, Kyathanahalli S. and Breen, Matthew and Mariani, Christopher L.}, year={2022}, month={Jul} }
 @article{lewis_thomas_breen_peden_teferedegne_foseh_motsinger-reif_rotroff_lewis_2022, title={The AGMK1-9T7 cell model of neoplasia: Evolution of DNA copy-number aberrations and miRNA expression during transition from normal to metastatic cancer cells}, volume={17}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0275394}, abstractNote={To study neoplasia in tissue culture, cell lines representing the evolution of normal cells to tumor cells are needed. To produce such cells, we developed the AGMK1-9T7 cell line, established cell banks at 10-passage intervals, and characterized their biological properties. Here we examine the evolution of chromosomal DNA copy-number aberrations and miRNA expression in this cell line from passage 1 to the acquisition of a tumorigenic phenotype at passage 40. We demonstrated the use of a human microarray platform for DNA copy-number profiling of AGMK1-9T7 cells using knowledge of synteny to ‘recode’ data from human chromosome coordinates to those of the African green monkey. This approach revealed the accumulation of DNA copy-number gains and losses in AGMK1-9T7 cells from passage 3 to passage 40, which spans the period in which neoplastic transformation occurred. These alterations occurred in the sequences of genes regulating DNA copy-number imbalance of several genes that regulate endothelial cell angiogenesis, survival, migration, and proliferation. Regarding miRNA expression, 195 miRNAs were up- or down-regulated at passage 1 at levels that appear to be biologically relevant (i.e., log2 fold change >2.0 (q<0.05)). At passage 10, the number of up/down-regulated miRNAs fell to 63; this number increased to 93 at passage 40. Principal-component analysis grouped these miRNAs into 3 clusters; miRNAs in sub-clusters of these groups could be correlated with initiation, promotion, and progression, stages that have been described for neoplastic development. Thirty-four of the AGMK1-9T7 miRNAs have been associated with these stages in human cancer. Based on these data, we propose that the evolution of AGMK1-9T7 cells represents a detailed model of neoplasia in vitro.}, number={10}, journal={PLOS ONE}, author={Lewis, Andrew M., Jr. and Thomas, Rachael and Breen, Matthew and Peden, Keith and Teferedegne, Belete and Foseh, Gideon and Motsinger-Reif, Alison and Rotroff, Daniel and Lewis, Gladys}, year={2022}, month={Oct} }
 @article{carlson_wcisel_ackerman_romanet_christiansen_niemuth_williams_breen_stoskopf_dornburg_et al._2022, title={Transcriptome annotation reveals minimal immunogenetic diversity among Wyoming toads, Anaxyrus baxteri}, volume={4}, ISSN={["1572-9737"]}, url={https://doi.org/10.1007/s10592-022-01444-8}, DOI={10.1007/s10592-022-01444-8}, abstractNote={Briefly considered extinct in the wild, the future of the Wyoming toad (Anaxyrus baxteri) continues to rely on captive breeding to supplement the wild population. Given its small natural geographic range and history of rapid population decline at least partly due to fungal disease, investigation of the diversity of key receptor families involved in the host immune response represents an important conservation need. Population decline may have reduced immunogenetic diversity sufficiently to increase the vulnerability of the species to infectious diseases. Here we use comparative transcriptomics to examine the diversity of toll-like receptors and major histocompatibility complex (MHC) sequences across three individual Wyoming toads. We find reduced diversity at MHC genes compared to bufonid species with a similar history of bottleneck events. Our data provide a foundation for future studies that seek to evaluate the genetic diversity of Wyoming toads, identify biomarkers for infectious disease outcomes, and guide breeding strategies to increase genomic variability and wild release successes.}, journal={CONSERVATION GENETICS}, author={Carlson, Kara B. and Wcisel, Dustin J. and Ackerman, Hayley D. and Romanet, Jessica and Christiansen, Emily F. and Niemuth, Jennifer N. and Williams, Christina and Breen, Matthew and Stoskopf, Michael K. and Dornburg, Alex and et al.}, year={2022}, month={Apr} }
 @article{wise_hammel_herkert_ospina_calafat_breen_stapleton_2021, title={Comparative Assessment of Pesticide Exposures in Domestic Dogs and Their Owners Using Silicone Passive Samplers and Biomonitoring}, ISSN={["1520-5851"]}, DOI={10.1021/acs.est.1c06819}, abstractNote={Pesticides are used extensively in residential settings for lawn maintenance and in homes to control household pests including application directly on pets to deter fleas and ticks. Pesticides are commonly detected in the home environment where people and pets can be subject to chronic exposure. Due to increased interest in using companion animals as sentinels for human environmental health studies, we conducted a comparative pesticide exposure assessment in 30 people and their pet dogs to determine how well silicone wristbands and silicone dog tags can predict urinary pesticide biomarkers of exposure. Using targeted gas chromatography-mass spectrometry analyses, we quantified eight pesticides in silicone samplers and used a suspect screening approach for additional pesticides. Urine samples were analyzed for 15 pesticide metabolite biomarkers. Several pesticides were detected in >70% of silicone samplers including permethrin, N,N-diethyl-meta-toluamide (DEET), and chlorpyrifos. Significant and positive correlations were observed between silicone sampler levels of permethrin and DEET with their corresponding urinary metabolites (rs = 0.50-0.96, p < 0.05) in both species. Significantly higher levels of fipronil were observed in silicone samplers from participants who reported using flea and tick products containing fipronil on their dog. This study suggests that people and their dogs have similar pesticide exposures in a home environment.}, journal={ENVIRONMENTAL SCIENCE & TECHNOLOGY}, author={Wise, Catherine F. and Hammel, Stephanie C. and Herkert, Nicholas J. and Ospina, Maria and Calafat, Antonia M. and Breen, Matthew and Stapleton, Heather M.}, year={2021}, month={Dec} }
 @article{kim_megquier_thomas_sarver_song_kim_cheng_schulte_linden_murugan_et al._2021, title={Genomically Complex Human Angiosarcoma and Canine Hemangiosarcoma Establish Convergent Angiogenic Transcriptional Programs Driven by Novel Gene Fusions}, volume={19}, ISSN={["1557-3125"]}, DOI={10.1158/1541-7786.MCR-20-0937}, abstractNote={Abstract}, number={5}, journal={MOLECULAR CANCER RESEARCH}, author={Kim, Jong Hyuk and Megquier, Kate and Thomas, Rachael and Sarver, Aaron L. and Song, Jung Min and Kim, Yoon Tae and Cheng, Nuojin and Schulte, Ashley J. and Linden, Michael A. and Murugan, Paari and et al.}, year={2021}, month={May}, pages={847–861} }
 @article{peart_williams_pophaly_neely_gulland_adams_ng_cheng_goebel_fedrigo_et al._2021, title={Hi-C scaffolded short- and long-read genome assemblies of the California sea lion are broadly consistent for syntenic inference across 45 million years of evolution}, ISSN={["1755-0998"]}, DOI={10.1111/1755-0998.13443}, abstractNote={Abstract}, journal={MOLECULAR ECOLOGY RESOURCES}, author={Peart, Claire R. and Williams, Christina and Pophaly, Saurabh D. and Neely, Benjamin A. and Gulland, Frances M. D. and Adams, David J. and Ng, Bee Ling and Cheng, William and Goebel, Michael E. and Fedrigo, Olivier and et al.}, year={2021}, month={Jun} }
 @article{rossman_zabka_ruple_tuerck_ramos-vara_liu_mohallem_merchant_franco_fulkerson_et al._2021, title={Phase I/II Trial of Vemurafenib in Dogs with Naturally Occurring, BRAF-mutated Urothelial Carcinoma}, volume={20}, ISSN={["1538-8514"]}, DOI={10.1158/1535-7163.MCT-20-0893}, abstractNote={Abstract}, number={11}, journal={MOLECULAR CANCER THERAPEUTICS}, author={Rossman, Paul and Zabka, Tanja S. and Ruple, Audrey and Tuerck, Dietrich and Ramos-Vara, Jose A. and Liu, Liling and Mohallem, Rodrigo and Merchant, Mark and Franco, Jackeline and Fulkerson, Christopher M. and et al.}, year={2021}, month={Nov}, pages={2177–2188} }
 @article{tawa_braisted_gerhold_grewal_mazcko_breen_sittampalam_leblanc_2021, title={Transcriptomic profiling in canines and humans reveals cancer specific gene modules and biological mechanisms common to both species}, volume={17}, ISSN={["1553-7358"]}, DOI={10.1371/journal.pcbi.1009450}, abstractNote={Understanding relationships between spontaneous cancer in companion (pet) canines and humans can facilitate biomarker and drug development in both species. Towards this end we developed an experimental-bioinformatic protocol that analyzes canine transcriptomics data in the context of existing human data to evaluate comparative relevance of canine to human cancer. We used this protocol to characterize five canine cancers: melanoma, osteosarcoma, pulmonary carcinoma, B- and T-cell lymphoma, in 60 dogs. We applied an unsupervised, iterative clustering method that yielded five co-expression modules and found that each cancer exhibited a unique module expression profile. We constructed cancer models based on the co-expression modules and used the models to successfully classify the canine data. These canine-derived models also successfully classified human tumors representing the same cancers, indicating shared cancer biology between canines and humans. Annotation of the module genes identified cancer specific pathways relevant to cells-of-origin and tumor biology. For example, annotations associated with melanin production (PMEL,GPNMB, andBACE2), synthesis of bone material (COL5A2,COL6A3, andCOL12A1), synthesis of pulmonary surfactant (CTSH,LPCAT1, andNAPSA), ribosomal proteins (RPL8,RPS7, andRPLP0), and epigenetic regulation (EDEM1,PTK2B, andJAK1) were unique to melanoma, osteosarcoma, pulmonary carcinoma, B- and T-cell lymphoma, respectively. In total, 152 biomarker candidates were selected from highly expressing modules for each cancer type. Many of these biomarker candidates are under-explored as drug discovery targets and warrant further study. The demonstrated transferability of classification models from canines to humans enforces the idea that tumor biology, biomarker targets, and associated therapeutics, discovered in canines, may translate to human medicine.}, number={9}, journal={PLOS COMPUTATIONAL BIOLOGY}, author={Tawa, Gregory J. and Braisted, John and Gerhold, David and Grewal, Gurmit and Mazcko, Christina and Breen, Matthew and Sittampalam, Gurusingham and LeBlanc, Amy K.}, year={2021}, month={Sep} }
 @article{leblanc_mazcko_breen_thomas_thamm_2020, title={A comparative oncology approach to biomarker and drug discovery for cancer diagnosis and treatment in dogs and humans}, volume={80}, ISSN={["1538-7445"]}, DOI={10.1158/1538-7445.AM2020-6134}, abstractNote={Abstract}, number={16}, journal={CANCER RESEARCH}, author={LeBlanc, Amy Kathleen and Mazcko, Christina N. and Breen, Matthew and Thomas, Rachael and Thamm, Douglas H.}, year={2020}, month={Aug} }
 @article{wise_hammel_herkert_ma_motsinger-reif_stapleton_breen_2020, title={Comparative Exposure Assessment Using Silicone Passive Samplers Indicates That Domestic Dogs Are Sentinels To Support Human Health Research}, volume={54}, ISSN={["1520-5851"]}, DOI={10.1021/acs.est.9b06605}, abstractNote={Silicone wristbands are promising passive samplers to support epidemiology studies in characterizing exposure to organic contaminants; however, investigating associated health risks remains challenging due to the latency period for many chronic diseases that take years to manifest. Dogs provide valuable insights as sentinels for exposure-related human disease because they share similar exposures in the home, have shorter lifespans, share many clinical/biological features, and have closely related genomes. Here, we evaluated exposures among pet dogs and their owners using silicone dog tags and wristbands to determine if contaminant levels were correlated with validated biomarkers. Significant correlations between measures on dog tags and wristbands were observed (rs = 0.38-0.90; p <0.05). Correlations with urinary biomarkers were often stronger in dog tags compared to human wristbands (rs = 0.50-0.71; p <0.01) for several organophosphate esters. This supports the value of using silicone bands with dogs to investigate health impacts on humans from shared exposures.}, number={12}, journal={ENVIRONMENTAL SCIENCE & TECHNOLOGY}, author={Wise, Catherine F. and Hammel, Stephanie C. and Herkert, Nicholas and Ma, Jun and Motsinger-Reif, Alison and Stapleton, Heather M. and Breen, Matthew}, year={2020}, month={Jun}, pages={7409–7419} }
 @article{thomas_pontius_borst_breen_2020, title={Development of a Genome-Wide Oligonucleotide Microarray Platform for Detection of DNA Copy Number Aberrations in Feline Cancers}, volume={7}, ISSN={["2306-7381"]}, DOI={10.3390/vetsci7030088}, abstractNote={The utility of the domestic cat as a model system for biomedical studies was constrained for many years by the absence of a comprehensive feline reference genome sequence assembly. While such a resource now exists, the cat continues to lag behind the domestic dog in terms of integration into the ‘One Health’ era of molecular medicine. Stimulated by the advances being made within the evolving field of comparative cancer genomics, we developed a microarray platform that allows rapid and sensitive detection of DNA copy number aberrations in feline tumors using comparative genomic hybridization analysis. The microarray comprises 110,456 unique oligonucleotide probes anchored at mean intervals of 22.6 kb throughout the feline reference genome sequence assembly, providing ~350-fold higher resolution than was previously possible using this technique. We demonstrate the utility of this resource through genomic profiling of a feline injection-site sarcoma case, revealing a highly disrupted profile of DNA copy number imbalance involving several key cancer-associated genes including KIT, TP53, PTEN, FAS and RB1. These findings were supported by targeted fluorescence in-situ hybridization analysis, which identified major alterations in chromosome structure, including complex intrachromosomal reorganization events typical of those seen in aggressive soft-tissue sarcomas of other species. We then characterized a second mass that was identified at a nearby site in the same patient almost 12 months later. This mass demonstrated a remarkably conserved genomic profile consistent with a recurrence of the original tumor; however the detection of subtle differences reflected evolution of the tumor over time. These findings exemplify the diverse potential of this microarray platform to incorporate domestic cat cancers into comparative and translational research efforts in molecular oncology.}, number={3}, journal={VETERINARY SCIENCES}, author={Thomas, Rachael and Pontius, Joan U. and Borst, Luke B. and Breen, Matthew}, year={2020}, month={Sep} }
 @article{kim_megquier_sarver_thomas_schulte_wang_elvers_karlsson_breen_lindblad-toh_et al._2020, title={Molecular mechanisms that activate convergent oncogenic pathway in genomically complex angiosarcoma}, volume={80}, ISSN={["1538-7445"]}, DOI={10.1158/1538-7445.AM2020-195}, abstractNote={Abstract}, number={16}, journal={CANCER RESEARCH}, author={Kim, Jong Hyuk and Megquier, Kate and Sarver, Aaron L. and Thomas, Rachael and Schulte, Ashley J. and Wang, Chao and Elvers, Ingegerd and Karlsson, Elinor and Breen, Matthew and Lindblad-Toh, Kerstin and et al.}, year={2020}, month={Aug} }
 @article{hedan_rault_abadie_ulve_botherel_devauchelle_copie-bergman_cadieu_parrens_alten_et al._2020, title={PTPN11mutations in canine and human disseminated histiocytic sarcoma}, volume={147}, ISSN={["1097-0215"]}, DOI={10.1002/ijc.32991}, abstractNote={In humans, histiocytic sarcoma (HS) is an aggressive cancer involving histiocytes. Its rarity and heterogeneity explain that treatment remains a challenge. Sharing high clinical and histopathological similarities with human HS, the canine HS is conversely frequent in specific breeds and thus constitutes a unique spontaneous model for human HS to decipher the genetic bases and to explore therapeutic options. We identified sequence alterations in the MAPK pathway in at least 63.9% (71/111) of HS cases with mutually exclusive BRAF (0.9%; 1/111), KRAS (7.2%; 8/111) and PTPN11 (56.75%; 63/111) mutations concentrated at hotspots common to human cancers. Recurrent PTPN11 mutations are associated to visceral disseminated HS subtype in dogs, the most aggressive clinical presentation. We then identified PTPN11 mutations in 3/19 (15.7%) human HS patients. Thus, we propose PTPN11 mutations as key events for a specific subset of human and canine HS: the visceral disseminated form. Finally, by testing drugs targeting the MAPK pathway in eight canine HS cell lines, we identified a better anti‐proliferation activity of MEK inhibitors than PTPN11 inhibitors in canine HS neoplastic cells. In combination, these results illustrate the relevance of naturally affected dogs in deciphering genetic mechanisms and selecting efficient targeted therapies for such rare and aggressive cancers in humans.}, number={6}, journal={INTERNATIONAL JOURNAL OF CANCER}, author={Hedan, Benoit and Rault, Melanie and Abadie, Jerome and Ulve, Ronan and Botherel, Nadine and Devauchelle, Patrick and Copie-Bergman, Christiane and Cadieu, Edouard and Parrens, Marie and Alten, Julia and et al.}, year={2020}, month={Sep}, pages={1657–1665} }
 @article{allwood_fierer_dunn_breen_reich_laber_clifton_grantham_faith_2020, title={Use of standardized bioinformatics for the analysis of fungal DNA signatures applied to sample provenance}, volume={310}, ISSN={["1872-6283"]}, DOI={10.1016/j.forsciint.2020.110250}, abstractNote={The use of environmental trace material to aid criminal investigations is an ongoing field of research within forensic science. The application of environmental material thus far has focused upon a variety of different objectives relevant to forensic biology, including sample provenance (also referred to as sample attribution). The capability to predict the provenance or origin of an environmental DNA sample would be an advantageous addition to the suite of investigative tools currently available. A metabarcoding approach is often used to predict sample provenance, through the extraction and comparison of the DNA signatures found within different environmental materials, such as the bacteria within soil or fungi within dust. Such approaches are combined with bioinformatics workflows and statistical modelling, often as part of large-scale study, with less emphasis on the investigation of the adaptation of these methods to a smaller scale method for forensic use. The present work was investigating a small-scale approach as an adaptation of a larger metabarcoding study to develop a model for global sample provenance using fungal DNA signatures collected from dust swabs. This adaptation was to facilitate a standardized method for consistent, reproducible sample treatment, including bioinformatics processing and final application of resulting data to the available prediction model. To investigate this small-scale method, 76 DNA samples were treated as anonymous test samples and analyzed using the standardized process to demonstrate and evaluate processing and customized sequence data analysis. This testing included samples originating from countries previously used to train the model, samples artificially mixed to represent multiple or mixed countries, as well as outgroup samples. Positive controls were also developed to monitor laboratory processing and bioinformatics analysis. Through this evaluation we were able to demonstrate that the samples could be processed and analyzed in a consistent manner, facilitated by a relatively user-friendly bioinformatic pipeline for sequence data analysis. Such investigation into standardized analyses and application of metabarcoding data is of key importance for the future use of applied microbiology in forensic science.}, journal={FORENSIC SCIENCE INTERNATIONAL}, author={Allwood, Julia S. and Fierer, Noah and Dunn, Robert R. and Breen, Matthew and Reich, Brian J. and Laber, Eric B. and Clifton, Jesse and Grantham, Neal S. and Faith, Seth A.}, year={2020}, month={May} }
 @article{megquier_turner-maier_swofford_kim_sarver_wang_sakthikumar_johnson_koltookian_lewellen_et al._2019, title={Comparative Genomics Reveals Shared Mutational Landscape in Canine Hemangiosarcoma and Human Angiosarcoma}, volume={17}, ISSN={["1557-3125"]}, DOI={10.1158/1541-7786.MCR-19-0221}, abstractNote={Abstract}, number={12}, journal={MOLECULAR CANCER RESEARCH}, author={Megquier, Kate and Turner-Maier, Jason and Swofford, Ross and Kim, Jong-Hyuk and Sarver, Aaron L. and Wang, Chao and Sakthikumar, Sharadha and Johnson, Jeremy and Koltookian, Michele and Lewellen, Mitzi and et al.}, year={2019}, month={Dec}, pages={2410–2421} }
 @article{kennedy_thomas_durrant_jiang_motsinger-reif_breen_2019, title={Genome-wide DNA copy number analysis and targeted transcriptional analysis of canine histiocytic malignancies identifies diagnostic signatures and highlights disruption of spindle assembly complex}, volume={27}, ISSN={["1573-6849"]}, DOI={10.1007/s10577-019-09606-0}, abstractNote={Canine histiocytic malignancies (HM) are rare across the general dog population, but overrepresented in certain breeds, such as Bernese mountain dog and flat-coated retriever. Accurate diagnosis relies on immunohistochemical staining to rule out histologically similar cancers with different prognoses and treatment strategies (e.g., lymphoma and hemangiosarcoma). HM are generally treatment refractory with overall survival of less than 6 months. A lack of understanding regarding the mechanisms of disease development and progression hinders development of novel therapeutics. While the study of human tumors can benefit veterinary medicine, the rarity of the suggested orthologous disease (dendritic cell sarcoma) precludes this. This study aims to improve the understanding of underlying disease mechanisms using genome-wide DNA copy number and gene expression analysis of spontaneous HM across several dog breeds. Extensive DNA copy number disruption was evident, with losses of segments of chromosomes 16 and 31 detected in 93% and 72% of tumors, respectively. Droplet digital PCR (ddPCR) evaluation of these regions in numerous cancer specimens effectively discriminated HM from other common round cell tumors, including lymphoma and hemangiosarcoma, resulting in a novel, rapid diagnostic aid for veterinary medicine. Transcriptional analysis demonstrated disruption of the spindle assembly complex, which is linked to genomic instability and reduced therapeutic impact in humans. A key signature detected was up-regulation of Matrix Metalloproteinase 9 (MMP9), supported by an immunohistochemistry-based assessment of MMP9 protein levels. Since MMP9 has been linked with rapid metastasis and tumor aggression in humans, the data in this study offer a possible mechanism of aggression in HM.}, number={3}, journal={CHROMOSOME RESEARCH}, author={Kennedy, Katherine and Thomas, Rachael and Durrant, Jessica and Jiang, Tao and Motsinger-Reif, Alison and Breen, Matthew}, year={2019}, month={Sep}, pages={179–202} }
 @article{fisher_levine_guy_mochizuki_breen_schal_watson_2019, title={Lack of influence by endosymbiont Wolbachia on virus titer in the common bed bug, Cimex lectularius}, volume={12}, ISSN={1756-3305}, url={http://dx.doi.org/10.1186/s13071-019-3694-2}, DOI={10.1186/s13071-019-3694-2}, abstractNote={Abstract}, number={1}, journal={Parasites & Vectors}, publisher={Springer Science and Business Media LLC}, author={Fisher, Michael L. and Levine, Jay F. and Guy, James S. and Mochizuki, Hiroyuki and Breen, Matthew and Schal, Coby and Watson, David W.}, year={2019}, month={Sep} }
 @article{wiley_wise_breen_2019, title={Novel Noninvasive Diagnostics}, volume={49}, ISSN={["1878-1306"]}, DOI={10.1016/j.cvsm.2019.05.002}, abstractNote={Molecular diagnostics have revolutionized human oncology to allow early detection, targeted therapy, monitoring throughout treatment, and evidence of recurrence. By identifying genetic signatures associated with cancers, liquid biopsy techniques have been developed to diagnose and monitor cancer in noninvasive or minimally invasive ways. These techniques offer new opportunities for improving cancer screening, diagnosis, and monitoring the impact of therapy on the patients over time. Liquid biopsy also drives drug development programs. Similar diagnostics hold promise for comparable results in the veterinary field. Several noninvasive/minimally invasive techniques have been described in veterinary medicine that could be referred to as liquid biopsy.}, number={5}, journal={VETERINARY CLINICS OF NORTH AMERICA-SMALL ANIMAL PRACTICE}, author={Wiley, Claire and Wise, Catherine F. and Breen, Matthew}, year={2019}, month={Sep}, pages={781-+} }
 @article{palkopoulou_lipson_mallick_nielsen_rohland_baleka_karpinski_ivancevic_to_kortschak_et al._2018, title={A comprehensive genomic history of extinct and living elephants}, volume={115}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/PNAS.1720554115}, DOI={10.1073/PNAS.1720554115}, abstractNote={Significance}, number={11}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Palkopoulou, Eleftheria and Lipson, Mark and Mallick, Swapan and Nielsen, Svend and Rohland, Nadin and Baleka, Sina and Karpinski, Emil and Ivancevic, Atma M. and To, Thu-Hien and Kortschak, R. Daniel and et al.}, year={2018}, month={Feb}, pages={E2566–E2574} }
 @article{sarver_mills_temiz_scott_sarver_spector_wang_breen_subramanian_moriarity_et al._2018, title={Comparative genomic analyses of osteosarcoma etiology reveal a chromosomal structural rationale for the increased incidence of osteosarcoma in dogs}, volume={78}, ISSN={["1538-7445"]}, DOI={10.1158/1538-7445.AM2018-3399}, abstractNote={Abstract}, number={13}, journal={CANCER RESEARCH}, author={Sarver, Aaron L. and Mills, Lauren and Temiz, Nuri and Scott, MIlcah and Sarver, Anne and Spector, Logan and Wang, Jinhua and Breen, Mathew and Subramanian, Subbaya and Moriarity, Branden and et al.}, year={2018}, month={Jul} }
 @article{fisher_watson_osborne_mochizuki_breen_schal_2018, title={Growth kinetics of endosymbiont Wolbachia in the common bed bug, Cimex lectularius}, volume={8}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/S41598-018-29682-2}, DOI={10.1038/S41598-018-29682-2}, abstractNote={Abstract}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Fisher, Michael L. and Watson, David W. and Osborne, Jason A. and Mochizuki, Hiroyuki and Breen, Matthew and Schal, Coby}, year={2018}, month={Jul} }
 @article{kim_megquier_sarver_thomas_wang_elvers_karlsson_breen_lindblad-toh_modiano_2018, title={Mutational and transcriptomic profiling identify distinct angiogenic and inflammatory subtypes of angiosarcoma}, volume={78}, ISSN={["1538-7445"]}, DOI={10.1158/1538-7445.AM2018-5357}, abstractNote={Abstract}, number={13}, journal={CANCER RESEARCH}, author={Kim, Jong Hyuk and Megquier, Kate and Sarver, Aaron L. and Thomas, Rachael and Wang, Chao and Elvers, Ingegerd and Karlsson, Elinor and Breen, Matthew and Lindblad-Toh, Kerstin and Modiano, Jaime F.}, year={2018}, month={Jul} }
 @article{dumont_williams_ng_horncastle_chambers_mcgraw_adams_mackay_breen_2018, title={Relationship Between Sequence Homology, Genome Architecture, and Meiotic Behavior of the Sex Chromosomes in North American Voles}, volume={210}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.118.301182}, abstractNote={Abstract}, number={1}, journal={GENETICS}, author={Dumont, Beth L. and Williams, Christina L. and Ng, Bee Ling and Horncastle, Valerie and Chambers, Carol L. and McGraw, Lisa A. and Adams, David and Mackay, Trudy F. C. and Breen, Matthew}, year={2018}, month={Sep}, pages={83–97} }
 @article{hendricks_zismann_sivaprakasam_legendre_poorman_tembe_perdigones_kiefer_liang_deluca_et al._2018, title={Somatic inactivating PTPRJ mutations and dysregulated pathways identified in canine malignant melanoma by integrated comparative genomic analysis}, volume={14}, ISSN={["1553-7404"]}, DOI={10.1371/journal.pgen.1007589}, abstractNote={Canine malignant melanoma, a significant cause of mortality in domestic dogs, is a powerful comparative model for human melanoma, but little is known about its genetic etiology. We mapped the genomic landscape of canine melanoma through multi-platform analysis of 37 tumors (31 mucosal, 3 acral, 2 cutaneous, and 1 uveal) and 17 matching constitutional samples including long- and short-insert whole genome sequencing, RNA sequencing, array comparative genomic hybridization, single nucleotide polymorphism array, and targeted Sanger sequencing analyses. We identified novel predominantly truncating mutations in the putative tumor suppressor gene PTPRJ in 19% of cases. No BRAF mutations were detected, but activating RAS mutations (24% of cases) occurred in conserved hotspots in all cutaneous and acral and 13% of mucosal subtypes. MDM2 amplifications (24%) and TP53 mutations (19%) were mutually exclusive. Additional low-frequency recurrent alterations were observed amidst low point mutation rates, an absence of ultraviolet light mutational signatures, and an abundance of copy number and structural alterations. Mutations that modulate cell proliferation and cell cycle control were common and highlight therapeutic axes such as MEK and MDM2 inhibition. This mutational landscape resembles that seen in BRAF wild-type and sun-shielded human melanoma subtypes. Overall, these data inform biological comparisons between canine and human melanoma while suggesting actionable targets in both species.}, number={9}, journal={PLOS GENETICS}, author={Hendricks, William P. D. and Zismann, Victoria and Sivaprakasam, Karthigayini and Legendre, Christophe and Poorman, Kelsey and Tembe, Waibhav and Perdigones, Nieves and Kiefer, Jeffrey and Liang, Winnie and DeLuca, Valerie and et al.}, year={2018}, month={Sep} }
 @article{mochizuki_motsinger-reif_bettini_moroff_breen_2017, title={Association of breed and histopathological grade in canine mast cell tumours}, volume={15}, ISSN={["1476-5829"]}, url={http://europepmc.org/abstract/med/27198171}, DOI={10.1111/vco.12225}, abstractNote={Abstract}, number={3}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Mochizuki, H. and Motsinger-Reif, A. and Bettini, C. and Moroff, S. and Breen, M.}, year={2017}, month={Sep}, pages={829–839} }
 @article{seelig_ito_forster_yoon_breen_burns_bachanova_lindblad-toh_timothy d. o'brien_schmechel_et al._2017, title={Constitutive activation of alternative nuclear factor kappa B pathway in canine diffuse large B-cell lymphoma contributes to tumor cell survival and is a target of new adjuvant therapies}, volume={58}, ISSN={["1029-2403"]}, DOI={10.1080/10428194.2016.1260122}, abstractNote={Abstract Activation of the classical nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway is a common molecular event observed in both human and canine diffuse large B-cell lymphoma (DLBCL). Although the oncogenic potential of the alternative NFκB pathway (ANFκBP) has also been recently identified in DLBCL, its precise role in tumor pathogenesis and potential as a treatment target is understudied. We hypothesized that up-regulation of the ANFκBP plays an important role in the proliferation and survival of canine DLBCL cells, and we demonstrate that the ANFκBP is constitutively active in primary canine DLBCL samples and a cell line (CLBL1). We further demonstrate that a small interfering RNA inhibits the activation of the NFκB pathway and induces apoptosis in canine DLBCL cells. In conclusion, the ANFκBP facilitates survival of canine DLBCL cells, and thus, dogs with spontaneous DLBCL can provide a useful large animal model to study therapies targeting the ANFκBP.}, number={7}, journal={LEUKEMIA & LYMPHOMA}, author={Seelig, Davis M. and Ito, Daisuke and Forster, Colleen L. and Yoon, Una A. and Breen, Matthew and Burns, Linda J. and Bachanova, Veronika and Lindblad-Toh, Kerstin and Timothy D. O'Brien and Schmechel, Stephen C. and et al.}, year={2017}, pages={1702–1710} }
 @article{lim_koh_thomas_breen_olby_2017, title={Evaluation of gene expression and DNA copy number profiles of adipose tissue-derived stromal cells and consecutive neurosphere-like cells generated from dogs with naturally occurring spinal cord injury}, volume={78}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.78.3.371}, DOI={10.2460/ajvr.78.3.371}, abstractNote={Abstract}, number={3}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Lim, Ji-Hey and Koh, Sehwon and Thomas, Rachael and Breen, Matthew and Olby, Natasha J.}, year={2017}, month={Mar}, pages={371–380} }
 @article{gonçalves_bressan_roballo_meirelles_xavier_fukumasu_williams_breen_koh_sper_et al._2017, title={Generation of LIF-independent induced pluripotent stem cells from canine fetal fibroblasts}, volume={92}, ISSN={0093-691X}, url={http://dx.doi.org/10.1016/j.theriogenology.2017.01.013}, DOI={10.1016/j.theriogenology.2017.01.013}, abstractNote={Takahashi and Yamanaka established the first technique in which transcription factors related to pluripotency are incorporated into the genome of somatic cells to enable reprogramming of these cells. The expression of these transcription factors enables a differentiated somatic cell to reverse its phenotype to an embryonic state, generating induced pluripotent stem cells (iPSCs). iPSCs from canine fetal fibroblasts were produced through lentiviral polycistronic human and mouse vectors (hOSKM/mOSKM), aiming to obtain pluripotent stem cells with similar features to embryonic stem cells (ESC) in this animal model. The cell lines obtained in this study were independent of LIF or any other supplemental inhibitors, resistant to enzymatic procedure (TrypLE Express Enzyme), and dependent on bFGF. Clonal lines were obtained from slightly different protocols with maximum reprogramming efficiency of 0.001%. All colonies were positive for alkaline phosphatase, embryoid body formation, and spontaneous differentiation and expressed high levels of endogenous OCT4 and SOX2. Canine iPSCs developed tumors at 120 days post-injection in vivo. Preliminary chromosomal evaluations were performed by FISH hybridization, revealing no chromosomal abnormality. To the best of our knowledge, this report is the first to describe the ability to reprogram canine somatic cells via lentiviral vectors without supplementation and with resistance to enzymatic action, thereby demonstrating the pluripotency of these cell lines.}, journal={Theriogenology}, publisher={Elsevier BV}, author={Gonçalves, N.J.N. and Bressan, F.F. and Roballo, K.C.S. and Meirelles, F.V. and Xavier, P.L.P. and Fukumasu, H. and Williams, C. and Breen, M. and Koh, S. and Sper, R. and et al.}, year={2017}, month={Apr}, pages={75–82} }
 @article{mochizuki_thomas_moroff_breen_2017, title={Genomic profiling of canine mast cell tumors identifies DNA copy number aberrations associated with KIT mutations and high histological grade}, volume={25}, ISSN={["1573-6849"]}, url={http://europepmc.org/abstract/med/28058543}, DOI={10.1007/s10577-016-9543-7}, abstractNote={Mast cell tumor (MCT) is the most common skin malignancy of domestic dogs and presents with a widely variable clinical behavior. Although activating KIT mutations are present in approximately 20% of canine MCTs, molecular etiology is largely unknown for the majority of this cancer. Characterization of genomic alterations in canine MCTs may identify genomic regions and/or genes responsible for their development and progression, facilitating the discovery of new therapeutic targets and improved clinical management of this heterogeneous cancer. We performed genome-wide DNA copy number analysis of 109 primary MCTs derived from three popular canine breeds (the Boxer, Labrador Retriever, and Pug) as well as nontarget breeds using oligonucleotide array comparative genomic hybridization (oaCGH). We demonstrated a stepwise accumulation of numerical DNA copy number aberrations (CNAs) as tumor grade increases. DNA sequencing analysis revealed that KIT mutations were found less frequently in the Pug tumors and were strongly associated with high histological grade. Tumors with KIT mutations showed genome-wide aberrant copy number profiles, with frequent CNAs involving genes in the p53 and RB pathways, whereas CNAs were very limited in tumors with wild-type KIT. We evaluated the presence of four CNAs to predict aggressive tumor phenotypes. This approach predicted aggressive tumors with a sensitivity of 78-94% and specificity of 88-93%, when using oaCGH and droplet digital PCR platforms. Further investigation of genome regions identified in this study may lead to the development of a molecular tool for classification and prognosis, as well as identification of therapeutic target molecules.}, number={2}, journal={CHROMOSOME RESEARCH}, author={Mochizuki, Hiroyuki and Thomas, Rachael and Moroff, Scott and Breen, Matthew}, year={2017}, month={Jun}, pages={129–143} }
 @article{thomas_demeter_kennedy_borst_singh_valli_le boedec_breen_2017, title={Integrated immunohistochemical and DNA copy number profiling analysis provides insight into the molecular pathogenesis of canine follicular lymphoma}, volume={15}, ISSN={["1476-5829"]}, DOI={10.1111/vco.12227}, abstractNote={Abstract}, number={3}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Thomas, R. and Demeter, Z. and Kennedy, K. A. and Borst, L. and Singh, K. and Valli, V. E. and Le Boedec, K. and Breen, M.}, year={2017}, month={Sep}, pages={852–867} }
 @article{im_graef_breen_lindblad-toh_modiano_kim_2017, title={Interactions between CXCR4 and CXCL12 promote cell migration and invasion of canine hemangiosarcoma}, volume={15}, ISSN={["1476-5829"]}, DOI={10.1111/vco.12165}, abstractNote={Abstract}, number={2}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Im, K. S. and Graef, A. J. and Breen, M. and Lindblad-Toh, K. and Modiano, J. F. and Kim, J. -H.}, year={2017}, month={Jun}, pages={315–327} }
 @article{hensley_tang_woodruff_defrancesco_tou_williams_breen_meurs_keene_cheng_et al._2017, title={Intracoronary allogeneic cardiosphere-derived stem cells are safe for use in dogs with dilated cardiomyopathy}, volume={21}, ISSN={1582-1838}, url={http://dx.doi.org/10.1111/jcmm.13077}, DOI={10.1111/jcmm.13077}, abstractNote={Abstract}, number={8}, journal={Journal of Cellular and Molecular Medicine}, publisher={Wiley}, author={Hensley, Michael Taylor and Tang, Junnan and Woodruff, Kathleen and Defrancesco, Teresa and Tou, Sandra and Williams, Christina M. and Breen, Mathew and Meurs, Kathryn and Keene, Bruce and Cheng, Ke and et al.}, year={2017}, month={Mar}, pages={1503–1512} }
 @article{santos_dias-pereira_williams_lopes_breen_2017, title={Malignant canine mammary tumours: Preliminary genomic insights using oligonucleotide array comparative genomic hybridisation analysis}, volume={222}, ISSN={["1532-2971"]}, DOI={10.1016/j.tvjl.2017.03.005}, abstractNote={Neoplastic mammary disease in female dogs represents a major health concern for dog owners and veterinarians, but the genomic basis of the disease is poorly understood. In this study, we performed high resolution oligonucleotide array comparative genomic hybridisation (oaCGH) to assess genome wide DNA copy number changes in 10 malignant canine mammary tumours from seven female dogs, including multiple tumours collected at one time from each of three female dogs. In all but two tumours, genomic imbalances were detected, with losses being more common than gains. Canine chromosomes 9, 22, 26, 27, 34 and X were most frequently affected. Dissimilar oaCGH ratio profiles were observed in multiple tumours from the same dogs, providing preliminary evidence for probable independent pathogenesis. Analysis of adjacent samples of one tumour revealed regional differences in the number of genomic imbalances, suggesting heterogeneity within tumours.}, journal={VETERINARY JOURNAL}, author={Santos, Marta and Dias-Pereira, Patricia and Williams, Christina and Lopes, Carlos and Breen, Matthew}, year={2017}, month={Apr}, pages={68–71} }
 @article{mochizuki_breen_2017, title={Sequence analysis of RAS and RAF mutation hot spots in canine carcinoma}, volume={15}, ISSN={["1476-5829"]}, url={https://doi.org/10.1111/vco.12275}, DOI={10.1111/vco.12275}, abstractNote={Abstract}, number={4}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, publisher={Wiley-Blackwell}, author={Mochizuki, H. and Breen, M.}, year={2017}, month={Dec}, pages={1598–1605} }
 @article{roode_rotroff_richards_moore_motsinger-reif_okamura_mizuno_tsujimoto_suter_breen_2016, title={Comprehensive genomic characterization of five canine lymphoid tumor cell lines}, volume={12}, journal={BMC Veterinary Research}, author={Roode, S. C. and Rotroff, D. and Richards, K. L. and Moore, P. and Motsinger-Reif, A. and Okamura, Y. and Mizuno, T. and Tsujimoto, H. and Suter, S. E. and Breen, M.}, year={2016} }
 @article{mochizuki_shapiro_breen_pathology_2016, title={Detection of Copy Number Imbalance in Canine Urothelial Carcinoma With Droplet Digital Polymerase Chain Reaction}, volume={53}, ISSN={["1544-2217"]}, url={http://europepmc.org/abstract/med/26574558}, DOI={10.1177/0300985815614975}, abstractNote={ Urothelial carcinoma (UC) is the most common neoplasm of the canine urinary tract. Clinical presentation of UC is shared with several other, more common urinary tract disorders, and this often delays diagnosis of the UC. Definitive diagnosis of UC requires histopathologic examination of a biopsy specimen, but the cost and invasiveness for these diagnostic tests often result in most diagnoses being made on the basis of clinical findings, diagnostic imaging, and cytologic examination of urine sediment. Regardless of the diagnostic process used, most UCs currently are not diagnosed until they are at an advanced clinical stage and so are associated with poor prognosis. Improved methods for earlier and less invasive detection are needed. In a previous study, the authors demonstrated the presence of highly recurrent DNA copy number aberrations (CNAs) in canine UC and hypothesized that detection of these CNAs in tumor cells can be used as a molecular diagnostic for UC. In this study, a multiplexed droplet digital polymerase chain reaction (ddPCR) assay was detected to detect and quantify CNAs of specific regions of canine chromosomes 8, 13, 19, and 36. The assay was effective at differentiating 31 neoplastic and 25 nonneoplastic bladder tissues based on copy number, with 100% sensitivity and specificity in tissue samples. CNAs were also detected by ddPCR in 67% (12 of 18) of urine DNA specimens derived from UC patients. The findings show that ddPCR is a useful molecular technique to detect CNAs and may be used as a noninvasive molecular diagnostic test for canine UC. }, number={4}, journal={VETERINARY PATHOLOGY}, author={Mochizuki, Hiroyuki and Shapiro, S.G. and Breen, M. and pathology, Veterinary}, year={2016}, month={Jul}, pages={764–772} }
 @article{omeir_thomas_teferedegne_williams_foseh_macauley_brinster_beren_peden_breen_et al._2015, title={A novel canine kidney cell line model for the evaluation of neoplastic development: karyotype evolution associated with spontaneous immortalization and tumorigenicity}, volume={23}, ISSN={["1573-6849"]}, DOI={10.1007/s10577-015-9474-8}, abstractNote={The molecular mechanisms underlying spontaneous neoplastic transformation in cultured mammalian cells remain poorly understood, confounding recognition of parallels with the biology of naturally occurring cancer. The broad use of tumorigenic canine cell lines as research tools, coupled with the accumulation of cytogenomic data from naturally occurring canine cancers, makes the domestic dog an ideal system in which to investigate these relationships. We developed a canine kidney cell line, CKB1-3T7, which allows prospective examination of the onset of spontaneous immortalization and tumorigenicity. We documented the accumulation of cytogenomic aberrations in CKB1-3T7 over 24 months in continuous culture. The majority of aberrations emerged in parallel with key phenotypic changes in cell morphology, growth kinetics, and tumor incidence and latency. Focal deletion of CDKN2A/B emerged first, preceding the onset and progression of tumorigenic potential, and progressed to a homozygous deletion across the cell population during extended culture. Interestingly, CKB1-3T7 demonstrated a tumorigenic phenotype in vivo prior to exhibiting loss of contact inhibition in vitro. We also performed the first genome-wide characterization of the canine tumorigenic cell line MDCK, which also exhibited CDKN2A/B deletion. MDCK and CKB1-3T7 cells shared several additional aberrations that we have reported previously as being highly recurrent in spontaneous canine cancers, many of which, as with CDKN2A/B deletion, are evolutionarily conserved in their human counterparts. The conservation of these molecular events across multiple species, in vitro and in vivo, despite their contrasting karyotypic architecture, is a powerful indicator of a common mechanism underlying emerging neoplastic activity. Through integrated cytogenomic and phenotypic characterization of serial passages of CKB1-3T7 from initiation to development of a tumorigenic phenotype, we present a robust and readily accessible model (to be made available through the American Type Culture Collection) of spontaneous neoplastic transformation that overcomes many of the limitations of earlier studies.}, number={4}, journal={CHROMOSOME RESEARCH}, author={Omeir, R. and Thomas, R. and Teferedegne, B. and Williams, C. and Foseh, G. and Macauley, J. and Brinster, L. and Beren, J. and Peden, K. and Breen, M. and et al.}, year={2015}, month={Dec}, pages={663–680} }
 @article{mochizuki_kennedy_shapiro_breen_2015, title={BRAF Mutations in Canine Cancers}, volume={10}, ISSN={["1932-6203"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000355955300139&KeyUID=WOS:000355955300139}, DOI={10.1371/journal.pone.0129534}, abstractNote={Activating mutations of the BRAF gene lead to constitutive activation of the MAPK pathway. Although many human cancers carry the mutated BRAF gene, this mutation has not yet been characterized in canine cancers. As human and canine cancers share molecular abnormalities, we hypothesized that BRAF gene mutations also exist in canine cancers. To test this hypothesis, we sequenced the exon 15 of BRAF, mutation hot spot of the gene, in 667 canine primary tumors and 38 control tissues. Sequencing analysis revealed that a single nucleotide T to A transversion at nucleotide 1349 occurred in 64 primary tumors (9.6%), with particularly high frequency in prostatic carcinoma (20/25, 80%) and urothelial carcinoma (30/45, 67%). This mutation results in the amino acid substitution of glutamic acid for valine at codon 450 (V450E) of canine BRAF, corresponding to the most common BRAF mutation in human cancer, V600E. The evolutional conservation of the BRAF V600E mutation highlights the importance of MAPK pathway activation in neoplasia and may offer opportunity for molecular diagnostics and targeted therapeutics for dogs bearing BRAF-mutated cancers.}, number={6}, journal={PLOS ONE}, author={Mochizuki, Hiroyuki and Kennedy, Katherine and Shapiro, Susan G. and Breen, Matthew}, year={2015}, month={Jun} }
 @article{shapiro_raghunath_williams_motsinger-reif_cullen_liu_albertson_ruvolo_bergstrom lucas_jin_et al._2015, title={Canine urothelial carcinoma: genomically aberrant and comparatively relevant}, volume={23}, ISSN={0967-3849 1573-6849}, url={http://dx.doi.org/10.1007/S10577-015-9471-Y}, DOI={10.1007/s10577-015-9471-y}, abstractNote={Urothelial carcinoma (UC), also referred to as transitional cell carcinoma (TCC), is the most common bladder malignancy in both human and canine populations. In human UC, numerous studies have demonstrated the prevalence of chromosomal imbalances. Although the histopathology of the disease is similar in both species, studies evaluating the genomic profile of canine UC are lacking, limiting the discovery of key comparative molecular markers associated with driving UC pathogenesis. In the present study, we evaluated 31 primary canine UC biopsies by oligonucleotide array comparative genomic hybridization (oaCGH). Results highlighted the presence of three highly recurrent numerical aberrations: gain of dog chromosome (CFA) 13 and 36 and loss of CFA 19. Regional gains of CFA 13 and 36 were present in 97 % and 84 % of cases, respectively, and losses on CFA 19 were present in 77 % of cases. Fluorescence in situ hybridization (FISH), using targeted bacterial artificial chromosome (BAC) clones and custom Agilent SureFISH probes, was performed to detect and quantify these regions in paraffin-embedded biopsy sections and urine-derived urothelial cells. The data indicate that these three aberrations are potentially diagnostic of UC. Comparison of our canine oaCGH data with that of 285 human cases identified a series of shared copy number aberrations. Using an informatics approach to interrogate the frequency of copy number aberrations across both species, we identified those that had the highest joint probability of association with UC. The most significant joint region contained the gene PABPC1, which should be considered further for its role in UC progression. In addition, cross-species filtering of genome-wide copy number data highlighted several genes as high-profile candidates for further analysis, including CDKN2A, S100A8/9, and LRP1B. We propose that these common aberrations are indicative of an evolutionarily conserved mechanism of pathogenesis and harbor genes key to urothelial neoplasia, warranting investigation for diagnostic, prognostic, and therapeutic applications.}, number={2}, journal={Chromosome Research}, publisher={Springer Science and Business Media LLC}, author={Shapiro, S. G. and Raghunath, S. and Williams, C. and Motsinger-Reif, A. A. and Cullen, J. M. and Liu, T. and Albertson, D. and Ruvolo, M. and Bergstrom Lucas, A. and Jin, J. and et al.}, year={2015}, month={Mar}, pages={311–331} }
 @article{poorman_borst_moroff_roy_labelle_motsinger-reif_breen_2015, title={Comparative cytogenetic characterization of primary canine melanocytic lesions using array CGH and fluorescence in situ hybridization}, volume={23}, ISSN={["1573-6849"]}, DOI={10.1007/s10577-014-9444-6}, abstractNote={Melanocytic lesions originating from the oral mucosa or cutaneous epithelium are common in the general dog population, with up to 100,000 diagnoses each year in the USA. Oral melanoma is the most frequent canine neoplasm of the oral cavity, exhibiting a highly aggressive course. Cutaneous melanocytomas occur frequently, but rarely develop into a malignant form. Despite the differential prognosis, it has been assumed that subtypes of melanocytic lesions represent the same disease. To address the relative paucity of information about their genomic status, molecular cytogenetic analysis was performed on the three recognized subtypes of canine melanocytic lesions. Using array comparative genomic hybridization (aCGH) analysis, highly aberrant distinct copy number status across the tumor genome for both of the malignant melanoma subtypes was revealed. The most frequent aberrations included gain of dog chromosome (CFA) 13 and 17 and loss of CFA 22. Melanocytomas possessed fewer genome wide aberrations, yet showed a recurrent gain of CFA 20q15.3–17. A distinctive copy number profile, evident only in oral melanomas, displayed a sigmoidal pattern of copy number loss followed immediately by a gain, around CFA 30q14. Moreover, when assessed by fluorescence in situ hybridization (FISH), copy number aberrations of targeted genes, such as gain of c-MYC (80 % of cases) and loss of CDKN2A (68 % of cases), were observed. This study suggests that in concordance with what is known for human melanomas, canine melanomas of the oral mucosa and cutaneous epithelium are discrete and initiated by different molecular pathways.}, number={2}, journal={CHROMOSOME RESEARCH}, author={Poorman, Kelsey and Borst, Luke and Moroff, Scott and Roy, Siddharth and Labelle, Philippe and Motsinger-Reif, Alison and Breen, Matthew}, year={2015}, month={Jun}, pages={171–186} }
 @misc{schiffman_breen_2015, title={Comparative oncology: what dogs and other species can teach us about humans with cancer}, volume={370}, ISSN={["1471-2970"]}, DOI={10.1098/rstb.2014.0231}, abstractNote={Over 1.66 million humans (approx. 500/100 000 population rate) and over 4.2 million dogs (approx. 5300/100 000 population rate) are diagnosed with cancer annually in the USA. The interdisciplinary field of comparative oncology offers a unique and strong opportunity to learn more about universal cancer risk and development through epidemiology, genetic and genomic investigations. Working across species, researchers from human and veterinary medicine can combine scientific findings to understand more quickly the origins of cancer and translate these findings to novel therapies to benefit both human and animals. This review begins with the genetic origins of canines and their advantage in cancer research. We next focus on recent findings in comparative oncology related to inherited, or genetic, risk for tumour development. We then detail the somatic, or genomic, changes within tumours and the similarities between species. The shared cancers between humans and dogs that we discuss include sarcoma (osteosarcoma, soft tissue sarcoma, histiocytic sarcoma, hemangiosarcoma), haematological malignancies (lymphoma, leukaemia), bladder cancer, intracranial neoplasms (meningioma, glioma) and melanoma. Tumour risk in other animal species is also briefly discussed. As the field of genomics advances, we predict that comparative oncology will continue to benefit both humans and the animals that live among us.}, number={1673}, journal={PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES}, author={Schiffman, Joshua D. and Breen, Matthew}, year={2015}, month={Jul} }
 @article{mochizuki_shapiro_breen_2015, title={Detection of BRAF Mutation in Urine DNA as a Molecular Diagnostic for Canine Urothelial and Prostatic Carcinoma}, volume={10}, ISSN={["1932-6203"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000366903300038&KeyUID=WOS:000366903300038}, DOI={10.1371/journal.pone.0144170}, abstractNote={Urothelial carcinoma (UC) of the lower urinary tract and prostatic carcinoma (PC) are aggressive genitourinary cancers in dogs, characterized by invasion to surrounding tissues and high metastatic potential. Current diagnosis of canine UC and PC requires histopathological examination of a biopsy. Such specimens require specialized medical equipment and are invasive procedures, limiting the availability of diagnosis by histopathology for many canine patients. Access to a non-invasive means to confirm diagnosis is currently an unmet need. Recently, the canine BRAF V595E mutation was detected in ~80% of canine UCs and PCs. In this study, we developed a droplet digital PCR (ddPCR) assay for detection of the canine BRAF V595E mutation in canine urogenital tumors. The assay was evaluated in DNA samples prepared from biopsy specimens of UC (n = 48) and PC (n = 27), as well and non-neoplastic bladder epithelium (n = 38). In addition the assay was assessed for use with DNA isolated from free catch urine samples derived from canine patients with UC (n = 23), PC (n = 3), as well as from dogs with cystitis and healthy controls (n = 37). In all cases the sensitivity to detect the mutant allele was compared with conventional Sanger sequencing. ddPCR had superior sensitivity for detection of the V595E mutation: 75% of UC, 85% of PC, and 0% of control samples were mutation positive, respectively, and the V595E mutation was detected at a level as low as just 1 in 10,000 alleles (~0.01%). Furthermore, the ddPCR assay identified the mutation in free catch urine samples from 83% of canine UC and PC patients, demonstrating its utility as a non-invasive means of diagnosis. We have shown that ddPCR is a sensitive molecular technique with the potential to facilitate accurate and non-invasive means of canine UC and PC diagnosis.}, number={12}, journal={PLOS ONE}, author={Mochizuki, Hiroyuki and Shapiro, Susan G. and Breen, Matthew}, year={2015}, month={Dec} }
 @article{roode_rotroff_avery_suter_bienzle_schiffman_motsinger-reif_breen_2015, title={Genome-wide assessment of recurrent genomic imbalances in canine leukemia identifies evolutionarily conserved regions for subtype differentiation}, volume={23}, ISSN={0967-3849 1573-6849}, url={http://dx.doi.org/10.1007/s10577-015-9475-7}, DOI={10.1007/s10577-015-9475-7}, abstractNote={Leukemia in dogs is a heterogeneous disease with survival ranging from days to years, depending on the subtype. Strides have been made in both human and canine leukemia to improve classification and understanding of pathogenesis through immunophenotyping, yet classification and choosing appropriate therapy remains challenging. In this study, we assessed 123 cases of canine leukemia (28 ALLs, 24 AMLs, 25 B-CLLs, and 46 T-CLLs) using high-resolution oligonucleotide array comparative genomic hybridization (oaCGH) to detect DNA copy number alterations (CNAs). For the first time, such data were used to identify recurrent CNAs and inclusive genes that may be potential drivers of subtype-specific pathogenesis. We performed predictive modeling to identify CNAs that could reliably differentiate acute subtypes (ALL vs. AML) and chronic subtypes (B-CLL vs. T-CLL) and used this model to differentiate cases with up to 83.3 and 95.8 % precision, respectively, based on CNAs at only one to three genomic regions. In addition, CGH datasets for canine and human leukemia were compared to reveal evolutionarily conserved copy number changes between species, including the shared gain of HSA 21q in ALL and ∼25 Mb of shared gain of HSA 12 and loss of HSA 13q14 in CLL. These findings support the use of canine leukemia as a relevant in vivo model for human leukemia and justify the need to further explore the conserved genomic regions of interest for their clinical impact.}, number={4}, journal={Chromosome Research}, publisher={Springer Science and Business Media LLC}, author={Roode, Sarah C. and Rotroff, Daniel and Avery, Anne C. and Suter, Steven E. and Bienzle, Dorothee and Schiffman, Joshua D. and Motsinger-Reif, Alison and Breen, Matthew}, year={2015}, month={Jun}, pages={681–708} }
 @article{nunney_maley_breen_hochberg_schiffman_2015, title={Peto's paradox and the promise of comparative oncology}, volume={370}, ISSN={["1471-2970"]}, DOI={10.1098/rstb.2014.0177}, abstractNote={The past several decades have seen a paradigm shift with the integration of evolutionary thinking into studying cancer. The evolutionary lens is most commonly employed in understanding cancer emergence, tumour growth and metastasis, but there is an increasing realization that cancer defences both between tissues within the individual and between species have been influenced by natural selection. This special issue focuses on discoveries of these deeper evolutionary phenomena in the emerging area of ‘comparative oncology’. Comparing cancer dynamics in different tissues or species can lead to insights into how biology and ecology have led to differences in carcinogenesis, and the diversity, incidence and lethality of cancers. In this introduction to the special issue, we review the history of the field and outline how the contributions use empirical, comparative and theoretical approaches to address the processes and patterns associated with ‘Peto's paradox’, the lack of a statistical relationship of cancer incidence with body size and longevity. This burgeoning area of research can help us understand that cancer is not only a disease but is also a driving force in biological systems and species life histories. Comparative oncology will be key to understanding globally important health issues, including cancer epidemiology, prevention and improved therapies.}, number={1673}, journal={PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES}, author={Nunney, Leonard and Maley, Carlo C. and Breen, Matthew and Hochberg, Michael E. and Schiffman, Joshua D.}, year={2015}, month={Jul} }
 @article{simmons_dirksen_hildreth_dorr_williams_thomas_breen_toribio_rosol_2014, title={Canine Prostate Cancer Cell Line (Probasco) Produces Osteoblastic Metastases In Vivo}, volume={74}, ISSN={["1097-0045"]}, DOI={10.1002/pros.22838}, abstractNote={Abstract}, number={13}, journal={PROSTATE}, author={Simmons, Jessica K. and Dirksen, Wessel P. and Hildreth, Blake E., III and Dorr, Carlee and Williams, Christina and Thomas, Rachael and Breen, Matthew and Toribio, Ramiro E. and Rosol, Thomas J.}, year={2014}, month={Sep}, pages={1251–1265} }
 @article{sanderson_norman_guethlein_ellis_williams_breen_park_magee_babrzadeh_warry_et al._2014, title={Definition of the Cattle Killer Cell Ig-like Receptor Gene Family: Comparison with Aurochs and Human Counterparts}, volume={193}, ISSN={["1550-6606"]}, DOI={10.4049/jimmunol.1401980}, abstractNote={Abstract}, number={12}, journal={JOURNAL OF IMMUNOLOGY}, author={Sanderson, Nicholas D. and Norman, Paul J. and Guethlein, Lisbeth A. and Ellis, Shirley A. and Williams, Christina and Breen, Matthew and Park, Steven D. E. and Magee, David A. and Babrzadeh, Farbod and Warry, Andrew and et al.}, year={2014}, month={Dec}, pages={6016–6030} }
 @article{thomas_borst_rotroff_motsinger-reif_lindblad-toh_modiano_breen_2014, title={Genomic profiling reveals extensive heterogeneity in somatic DNA copy number aberrations of canine hemangiosarcoma}, volume={22}, ISSN={["1573-6849"]}, DOI={10.1007/s10577-014-9406-z}, abstractNote={Canine hemangiosarcoma is a highly aggressive vascular neoplasm associated with extensive clinical and anatomical heterogeneity and a grave prognosis. Comprehensive molecular characterization of hemangiosarcoma may identify novel therapeutic targets and advanced clinical management strategies, but there are no published reports of tumor-associated genome instability and disrupted gene dosage in this cancer. We performed genome-wide microarray-based somatic DNA copy number profiling of 75 primary intra-abdominal hemangiosarcomas from five popular dog breeds that are highly predisposed to this disease. The cohort exhibited limited global genomic instability, compared to other canine sarcomas studied to date, and DNA copy number aberrations (CNAs) were predominantly of low amplitude. Recurrent imbalances of several key cancer-associated genes were evident; however, the global penetrance of any single CNA was low and no distinct hallmark aberrations were evident. Copy number gains of dog chromosomes 13, 24, and 31, and loss of chromosome 16, were the most recurrent CNAs involving large chromosome regions, but their relative distribution within and between cases suggests they most likely represent passenger aberrations. CNAs involving CDKN2A, VEGFA, and the SKI oncogene were identified as potential driver aberrations of hemangiosarcoma development, highlighting potential targets for therapeutic modulation. CNA profiles were broadly conserved between the five breeds, although subregional variation was evident, including a near twofold lower incidence of VEGFA gain in Golden Retrievers versus other breeds (22 versus 40 %). These observations support prior transcriptional studies suggesting that the clinical heterogeneity of this cancer may reflect the existence of multiple, molecularly distinct subtypes of canine hemangiosarcoma.}, number={3}, journal={CHROMOSOME RESEARCH}, author={Thomas, Rachael and Borst, Luke and Rotroff, Daniel and Motsinger-Reif, Alison and Lindblad-Toh, Kerstin and Modiano, Jaime F. and Breen, Matthew}, year={2014}, month={Sep}, pages={305–319} }
 @article{gorden_kim_sarver_frantz_breen_lindblad-toh_timothy d. o'brien_sharkey_modiano_dickerson_2014, title={Identification of Three Molecular and Functional Subtypes in Canine Hemangiosarcoma through Gene Expression Profiling and Progenitor Cell Characterization}, volume={184}, ISSN={["1525-2191"]}, DOI={10.1016/j.ajpath.2013.12.025}, abstractNote={Canine hemangiosarcomas have been ascribed to an endothelial origin based on histologic appearance; however, recent findings suggest that these tumors may arise instead from hematopoietic progenitor cells. To clarify this ontogenetic dilemma, we used genome-wide expression profiling of primary hemangiosarcomas and identified three distinct tumor subtypes associated with angiogenesis (group 1), inflammation (group 2), and adipogenesis (group 3). Based on these findings, we hypothesized that a common progenitor may differentiate into the three tumor subtypes observed in our gene profiling experiment. To investigate this possibility, we cultured hemangiosarcoma cell lines under normal and sphere-forming culture conditions to enrich for tumor cell progenitors. Cells from sphere-forming cultures displayed a robust self-renewal capacity and exhibited genotypic, phenotypic, and functional properties consistent with each of the three molecular subtypes seen in primary tumors, including expression of endothelial progenitor cell (CD133 and CD34) and endothelial cell (CD105, CD146, and αvβ3 integrin) markers, expression of early hematopoietic (CD133, CD117, and CD34) and myeloid (CD115 and CD14) differentiation markers in parallel with increased phagocytic capacity, and acquisition of adipogenic potential. Collectively, these results suggest that canine hemangiosarcomas arise from multipotent progenitors that differentiate into distinct subtypes. Improved understanding of the mechanisms that determine the molecular and phenotypic differentiation of tumor cells in vivo could change paradigms regarding the origin and progression of endothelial sarcomas.}, number={4}, journal={AMERICAN JOURNAL OF PATHOLOGY}, author={Gorden, Brandi H. and Kim, Jong-Hyuk and Sarver, Aaron L. and Frantz, Aric M. and Breen, Matthew and Lindblad-Toh, Kerstin and Timothy D. O'Brien and Sharkey, Leslie C. and Modiano, Jaime F. and Dickerson, Erin B.}, year={2014}, month={Apr}, pages={985–995} }
 @article{su_nielsen_zhu_richards_suter_breen_motsinger-reif_osborne_2013, title={Gene selection and cancer type classification of diffuse large-B-cell lymphoma using a bivariate mixture model for two-species data}, volume={7}, journal={Human Genomics}, author={Su, Y. H. and Nielsen, D. and Zhu, L. and Richards, K. and Suter, S. and Breen, M. and Motsinger-Reif, A. and Osborne, J.}, year={2013} }
 @article{koh_thomas_tsai_bischoff_lim_breen_olby_piedrahita_2013, title={Growth Requirements and Chromosomal Instability of Induced Pluripotent Stem Cells Generated from Adult Canine Fibroblasts}, volume={22}, ISSN={1547-3287 1557-8534}, url={http://dx.doi.org/10.1089/scd.2012.0393}, DOI={10.1089/scd.2012.0393}, abstractNote={In mice and humans, it has been shown that embryonic and adult fibroblasts can be reprogrammed into pluripotency by introducing 4 transcription factors, Oct3/4, Klf4, Sox2, and c-Myc (OKSM). Here, we report the derivation of induced pluripotent stem cells (iPSCs) from adult canine fibroblasts by retroviral OKSM transduction. The isolated canine iPSCs (ciPSCs) were expanded in 3 different culture media [fibroblast growth factor 2 (FGF2), leukemia inhibitory factor (LIF), or FGF2 plus LIF]. Cells cultured in both FGF2 and LIF expressed pluripotency markers [POU5F1 (OCT4), SOX2, NANOG, and LIN28] and embryonic stem cell (ESC)-specific genes (PODXL, DPPA5, FGF5, REX1, and LAMP1) and showed strong levels of alkaline phosphatase expression. In vitro differentiation by formation of embryoid bodies and by directed differentiation generated cell derivatives of all 3 germ layers as confirmed by mRNA and protein expression. In vivo, the ciPSCs created solid tumors, which failed to reach epithelial structure formation, but expressed markers for all 3 germ layers. Array comparative genomic hybridization and chromosomal fluorescence in situ hybridization analyses revealed that while retroviral transduction per se did not result in significant DNA copy number imbalance, there was evidence for the emergence of low-level aneuploidy during prolonged culture or tumor formation. In summary, we were able to derive ciPSCs from adult fibroblasts by using 4 transcription factors. The isolated iPSCs have similar characteristics to ESCs from other species, but the exact cellular mechanisms behind their unique co-dependency on both FGF2 and LIF are still unknown.}, number={6}, journal={Stem Cells and Development}, publisher={Mary Ann Liebert Inc}, author={Koh, Sehwon and Thomas, Rachael and Tsai, Shengdar and Bischoff, Steve and Lim, Ji-Hey and Breen, Matthew and Olby, Natasha J. and Piedrahita, Jorge A.}, year={2013}, month={Mar}, pages={951–963} }
 @article{culver_ito_borst_bell_modiano_breen_2013, title={Molecular characterization of canine BCR-ABL-positive chronic myelomonocytic leukemia before and after chemotherapy}, volume={42}, ISSN={0275-6382}, url={http://dx.doi.org/10.1111/vcp.12055}, DOI={10.1111/vcp.12055}, abstractNote={Abstract}, number={3}, journal={Veterinary Clinical Pathology}, publisher={Wiley}, author={Culver, Sarah and Ito, Daisuke and Borst, Luke and Bell, Jerold S. and Modiano, Jaime F. and Breen, Matthew}, year={2013}, month={Jun}, pages={314–322} }
 @article{rotroff_thomas_breen_motsinger-reif_2013, title={Naturally occuring canine cancers: powerful models for stimulating pharmacogenomic advancement in human medicine}, volume={14}, ISSN={["1744-8042"]}, DOI={10.2217/pgs.13.178}, abstractNote={An estimated 1.6 million new cases of cancer were diagnosed in the USA in 2012 [101]. The pharmaceutical industry is working furiously to develop new efficacious chemotherapeutics; however, the vast majority of compounds that show anticancer activity in preclinical studies fail during subsequent human clinical trials, hindering progress in patient care and further increasing costs for drug development [1–3]. Modern cancer research places a heavy emphasis on murine models for investigating cancer etiology and for driving the development of new therapies. Mice represent excellent models for studying cancer due to their short lifespans, ease of maintenance and opportunities for genetic manipulation [4]. While their attributes have led to numerous fundamental advances in identifying novel therapies, several important limitations exist. Murine models of cancer are generally induced by genetic engineering, or by subcutaneous xenografts. The limitations and advantages of various methods of inducing neoplasms in mice are well reviewed elsewhere [4,5]. Induced murine neoplasms are developed in a short period of time and they lack heterogeneity in the tumor cell population, the microenvironment and the stroma, all of which are inconsistent with most human cancers. Furthermore, human cancers typically display increased genomic instability compared with their induced murine counterparts, which limits their utility as tools for pharmacogenomics [6]. Many of these limitations may be addressed by using the domestic dog as a complementary model system. Canines share our environment and develop many age-related diseases with similar pathologies to humans. Perhaps most importantly, dogs exhibit a wide variety of spontaneous cancers that share extensive clinicopathologic features with those of human patients, offering a unique opportunity for comparative analysis of}, number={16}, journal={PHARMACOGENOMICS}, author={Rotroff, Daniel M. and Thomas, Rachael and Breen, Matthew and Motsinger-Reif, Alison A.}, year={2013}, month={Dec}, pages={1929–1931} }
 @article{perez_culver_owen_dunbar_kow_breen_milner_2013, title={Partial cytogenetic response with toceranib and prednisone treatment in a young dog with chronic monocytic leukemia}, volume={24}, ISSN={["1473-5741"]}, DOI={10.1097/cad.0000000000000018}, abstractNote={Treatment of chronic monocytic leukemia (CMoL) in dogs has traditionally consisted of hydroxyurea. The use of tyrosine kinase inhibitors has been proposed as a treatment option for dogs with CMoL but has never been reported. We report a case of CMoL in a young dog that achieved clinical remission with treatment with the tyrosine kinase inhibitor toceranib and prednisone.}, number={10}, journal={ANTI-CANCER DRUGS}, author={Perez, Mayrim L. and Culver, Sarah and Owen, Jennifer L. and Dunbar, Mark and Kow, Kelvin and Breen, Matthew and Milner, Rowan J.}, year={2013}, month={Nov}, pages={1098–1103} }
 @article{angstadt_thayanithy_subramanian_modiano_breen_2012, title={A genome-wide approach to comparative oncology: high-resolution oligonucleotide aCGH of canine and human osteosarcoma pinpoints shared microaberrations}, volume={205}, ISSN={2210-7762}, url={http://dx.doi.org/10.1016/j.cancergen.2012.09.005}, DOI={10.1016/j.cancergen.2012.09.005}, abstractNote={Molecular cytogenetic evaluation of human osteosarcoma (OS) has revealed the characteristically high degree of genomic reorganization that is the hallmark of this cancer. The extent of genomic disorder in OS has hindered identification of the genomic aberrations driving disease progression. With pathophysiological similarities to its human counterpart, canine OS represents an ideal model for comparison of conserved regions of genomic instability that may be disease-associated rather than genomic passengers. This study used high-resolution oligonucleotide array comparative genomic hybridization and a variety of informatics tools to aid in the identification of disease-associated genome-wide DNA copy number aberrations in canine and human OS. Our findings support and build upon the high level of cytogenetic complexity, through the identification of shared regions of microaberration (<500 kb) and functional analysis of possible orthologous OS-associated genes to pinpoint the cellular processes most commonly affected by aberration in human and canine OS. Aberrant regions contained previously reported genes such as CDC5L, MYC, RUNX2, and CDKN2A/CDKN2B, while expanding the gene of interest list to include ADAM15, CTC1, MEN1, CDK7, and others. Such regions of instability may thus have functional significance in the etiology of OS, the most common primary bone tumor in both species.}, number={11}, journal={Cancer Genetics}, publisher={Elsevier BV}, author={Angstadt, Andrea Y. and Thayanithy, Venugopal and Subramanian, Subbaya and Modiano, Jaime F. and Breen, Matthew}, year={2012}, month={Nov}, pages={572–587} }
 @article{figueiredo_culver_behling-kelly_breen_friedrichs_2012, title={Acute myeloblastic leukemia with associated BCR-ABL translocation in a dog}, volume={41}, ISSN={["0275-6382"]}, DOI={10.1111/j.1939-165x.2012.00450.x}, abstractNote={Abstract}, number={3}, journal={VETERINARY CLINICAL PATHOLOGY}, author={Figueiredo, Josely F. and Culver, Sarah and Behling-Kelly, Erica and Breen, Matthew and Friedrichs, Kristen R.}, year={2012}, month={Sep}, pages={362–368} }
 @article{italiano_chen_thomas_breen_bonnet_sevenet_longy_maki_coindre_antonescu_2012, title={Alterations of the p53 and PIK3CA/AKT/mTOR pathways in angiosarcomas}, volume={118}, ISSN={0008-543X}, url={http://dx.doi.org/10.1002/cncr.27614}, DOI={10.1002/cncr.27614}, abstractNote={Abstract}, number={23}, journal={Cancer}, publisher={Wiley}, author={Italiano, Antoine and Chen, Chun-Liang and Thomas, Rachael and Breen, Matthew and Bonnet, Françoise and Sevenet, Nicolas and Longy, Michel and Maki, Robert G. and Coindre, Jean-Michel and Antonescu, Cristina R.}, year={2012}, month={May}, pages={5878–5887} }
 @article{tsai_breen_2012, title={Array-based comparative genomic hybridization-guided identification of reference genes for normalization of real-time quantitative polymerase chain reaction assay data for lymphomas, histiocytic sarcomas, and osteosarcomas of dogs}, volume={73}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.73.9.1335}, abstractNote={Abstract}, number={9}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Tsai, Pei-Chien and Breen, Matthew}, year={2012}, month={Sep}, pages={1335–1343} }
 @article{ito_frantz_williams_thomas_burnett_avery_breen_mason_timothy d. o'brien_modiano_2012, title={CD40 ligand is necessary and sufficient to support primary diffuse large B-cell lymphoma cells in culture: a tool for in vitro preclinical studies with primary B-cell malignancies}, volume={53}, ISSN={["1042-8194"]}, DOI={10.3109/10428194.2011.654337}, abstractNote={Abstract Established cell lines are utilized extensively to study tumor biology and preclinical therapeutic development. However, they may not accurately recapitulate the heterogeneity of their corresponding primary disease. B-cell tumor cells are especially difficult to maintain under conventional culture conditions, limiting access to samples that faithfully represent this disease for preclinical studies. Here, we used primary canine diffuse large B-cell lymphoma to establish a culture system that reliably supports the growth of these cells. CD40 ligand, either expressed by feeder cells or provided as a soluble two-trimeric form, was sufficient to support primary lymphoma cells in vitro. The tumor cells retained their original phenotype, clonality and known karyotypic abnormalities after extended expansion in culture. Finally, we illustrate the utility of the feeder cell-free culture system for comparable assessment of cytotoxicity using dog and human B-cell malignancies. We conclude that this system has broad applications for in vitro preclinical development for B-cell malignancies.}, number={7}, journal={LEUKEMIA & LYMPHOMA}, author={Ito, Daisuke and Frantz, Aric M. and Williams, Christina and Thomas, Rachael and Burnett, Robert C. and Avery, Anne C. and Breen, Matthew and Mason, Nicola J. and Timothy D. O'Brien and Modiano, Jaime F.}, year={2012}, month={Jul}, pages={1390–1398} }
 @inproceedings{koh_tsai_bischoff_thomas_lim_breen_olby_piedrahita_2012, title={Generation and characterization of induced pluripotent stem cells (iPS) from adult canine fibroblasts}, volume={47}, booktitle={Reproduction in Domestic Animals}, author={Koh, S. and Tsai, S. and Bischoff, S. and Thomas, R. and Lim, J. H. and Breen, M. and Olby, N. and Piedrahita, J.}, year={2012}, pages={418–419} }
 @article{thayanithy_sarver_kartha_li_angstadt_breen_steer_modiano_subramanian_2012, title={Perturbation of 14q32 miRNAs-cMYC gene network in osteosarcoma}, volume={50}, ISSN={["1873-2763"]}, DOI={10.1016/j.bone.2011.10.012}, abstractNote={Osteosarcoma (OS) is the common histological form of primary bone cancer and one of the leading aggressive cancers in children under age fifteen. Although several genetic predisposing conditions have been associated with OS the understanding of its molecular etiology is limited. Here, we show that microRNAs (miRNAs) at the chr.14q32 locus are significantly downregulated in osteosarcoma compared to normal bone tissues. Bioinformatic predictions identified that a subset of 14q32 miRNAs (miR-382, miR-369-3p, miR-544 and miR-134) could potentially target cMYC transcript. The physical interaction between these 14q32 miRNAs and cMYC was validated using reporter assays. Further, restoring expression of these four 14q32 miRNAs decreased cMYC levels and induced apoptosis in Saos2 cells. We also show that exogenous expression of 14q32 miRNAs in Saos2 cells significantly downregulated miR-17-92, a transcriptional target of cMYC. The pro-apoptotic effect of 14q32 miRNAs in Saos2 cells was rescued either by overexpression of cMYC cDNA without the 3'UTR or with miR-17-92 cluster. Further, array comparative genomic hybridization studies showed no DNA copy number changes at 14q32 locus in OS patient samples suggesting that downregulation of 14q32 miRNAs are not due to deletion at this locus. Together, our data support a model where the deregulation of a network involving 14q32 miRNAs, cMYC and miR-17-92 miRNAs could contribute to osteosarcoma pathogenesis.}, number={1}, journal={BONE}, author={Thayanithy, Venugopal and Sarver, Aaron L. and Kartha, Reena V. and Li, Lihua and Angstadt, Andrea Y. and Breen, Matthew and Steer, Clifford J. and Modiano, Jaime F. and Subramanian, Subbaya}, year={2012}, month={Jan}, pages={171–181} }
 @article{italiano_thomas_breen_zhang_crago_singer_khanin_maki_mihailovic_hafner_et al._2012, title={The miR-17-92 cluster and its target THBS1 are differentially expressed in angiosarcomas dependent on MYC amplification}, volume={51}, ISSN={["1098-2264"]}, DOI={10.1002/gcc.21943}, abstractNote={Abstract}, number={6}, journal={GENES CHROMOSOMES & CANCER}, author={Italiano, Antoine and Thomas, Rachael and Breen, Matthew and Zhang, Lei and Crago, Aimee M. and Singer, Samuel and Khanin, Raya and Maki, Robert G. and Mihailovic, Aleksandra and Hafner, Markus and et al.}, year={2012}, month={Jun}, pages={569–578} }
 @article{becker_thomas_trifonov_wayne_graphodatsky_breen_2011, title={Anchoring the dog to its relatives reveals new evolutionary breakpoints across 11 species of the Canidae and provides new clues for the role of B chromosomes}, volume={19}, ISSN={["1573-6849"]}, DOI={10.1007/s10577-011-9233-4}, abstractNote={The emergence of genome-integrated molecular cytogenetic resources allows for comprehensive comparative analysis of gross karyotype architecture across related species. The identification of evolutionarily conserved chromosome segment (ECCS) boundaries provides deeper insight into the process of chromosome evolution associated with speciation. We evaluated the genome-wide distribution and relative orientation of ECCSs in three wild canid species with diverse karyotypes (red fox, Chinese raccoon dog, and gray fox). Chromosome-specific panels of dog genome-integrated bacterial artificial chromosome (BAC) clones spaced at ∼10-Mb intervals were used in fluorescence in situ hybridization analysis to construct integrated physical genome maps of these three species. Conserved evolutionary breakpoint regions (EBRs) shared between their karyotypes were refined across these and eight additional wild canid species using targeted BAC panels spaced at ∼1-Mb intervals. Our findings suggest that the EBRs associated with speciation in the Canidae are compatible with recent phylogenetic groupings and provide evidence that these breakpoints are also recurrently associated with spontaneous canine cancers. We identified several regions of domestic dog sequence that share homology with canid B chromosomes, including additional cancer-associated genes, suggesting that these supernumerary elements may represent more than inert passengers within the cell. We propose that the complex karyotype rearrangements associated with speciation of the Canidae reflect unstable chromosome regions described by the fragile breakage model.}, number={6}, journal={CHROMOSOME RESEARCH}, author={Becker, Shannon E. Duke and Thomas, Rachael and Trifonov, Vladimir A. and Wayne, Robert K. and Graphodatsky, Alexander S. and Breen, Matthew}, year={2011}, month={Aug}, pages={685–708} }
 @article{cardona_milner_alleman_williams_vernau_breen_tompkins_2011, title={BCR-ABL translocation in a dog with chronic monocytic leukemia}, volume={40}, ISSN={["0275-6382"]}, DOI={10.1111/j.1939-165x.2010.00277.x}, abstractNote={Abstract:A 9‐year‐old female spayed mixed breed dog was evaluated at the University of Florida Small Animal Hospital for marked leukocytosis with no associated clinical signs. CBC abnormalities included marked leukocytosis (106,000/μL), marked monocytosis (78,000/μL), and the presence of 13% blast cells (13,832/μL), supporting a diagnosis of leukemia. Cytopenias and dysplastic changes in other cell lines were not present. Microscopic examination of bone marrow showed hypercellular uniparticles with a marginal increase in frequency of unclassified blast cells (2%), but was otherwise unremarkable. Flow cytometric immunophenotyping of blood cells determined that leukemic cells were CD45+, CD14+, and CD34–, and based on side scatter and CD45 reactivity the marrow contained 19% monoblasts. By immunocytochemical staining, the leukemic cells in the bone marrow were CD11b+, CD11c+, CD11d+, MHC‐II+, MPO+, and CD34–. Fluorescence in situ hybridization (FISH) analysis of peripheral blood leukocytes documented a chromosomal translocation producing a BCR‐ABL gene hybrid, similar to the “Philadelphia” chromosome abnormality recognized in human chronic myelogenous leukemia, as well as a phosphatase and tensin homolog (PTEN) gene deletion. Hydroxyurea therapy was attempted, but was ineffective; the dog died 7 months after initial presentation. Clinical and laboratory findings and the protracted course supported a diagnosis of chronic monocytic leukemia (CMoL) and, to our knowledge, this is the first case of CMoL with a BCR‐ABL chromosomal abnormalitiy described in dogs. This may have clinical implications for treatment of dogs with chronic leukemias associated with particular genetic mutations. However, more case studies are needed to further characterize this disease.}, number={1}, journal={VETERINARY CLINICAL PATHOLOGY}, author={Cardona, Janice A. Cruz and Milner, Rowan and Alleman, A. Rick and Williams, Christina and Vernau, William and Breen, Matthew and Tompkins, Mary}, year={2011}, month={Mar}, pages={40–47} }
 @article{angstadt_motsinger-reif_thomas_kisseberth_couto_duval_nielsen_modiano_breen_2011, title={Characterization of Canine Osteosarcoma by Array Comparative Genomic Hybridization and RT-qPCR: Signatures of Genomic Imbalance in Canine Osteosarcoma Parallel the Human Counterpart}, volume={50}, ISSN={["1098-2264"]}, DOI={10.1002/gcc.20908}, abstractNote={Abstract}, number={11}, journal={GENES CHROMOSOMES & CANCER}, author={Angstadt, Andrea Y. and Motsinger-Reif, Alison and Thomas, Rachael and Kisseberth, William C. and Couto, C. Guillermo and Duval, Dawn L. and Nielsen, Dahlia M. and Modiano, Jaime F. and Breen, Matthew}, year={2011}, month={Nov}, pages={859–874} }
 @article{thudi_shu_martin_lanigan_nadella_van bokhoven_werbeck_simmons_murahari_kisseberth_et al._2011, title={Development of a Brain Metastatic Canine Prostate Cancer Cell Line}, volume={71}, ISSN={["1097-0045"]}, DOI={10.1002/pros.21341}, abstractNote={Abstract}, number={12}, journal={PROSTATE}, author={Thudi, Nanda K. and Shu, Sherry T. and Martin, Chelsea K. and Lanigan, Lisa G. and Nadella, Murali V. P. and Van Bokhoven, Adrie and Werbeck, Jillian L. and Simmons, Jessica K. and Murahari, Sridhar and Kisseberth, William C. and et al.}, year={2011}, month={Sep}, pages={1251–1263} }
 @article{suter_small_seiser_thomas_breen_richards_2011, title={FLT3 mutations in canine acute lymphocytic leukemia}, volume={11}, ISSN={["1471-2407"]}, DOI={10.1186/1471-2407-11-38}, abstractNote={Abstract}, journal={BMC CANCER}, author={Suter, Steven E. and Small, George W. and Seiser, Eric L. and Thomas, Rachael and Breen, Matthew and Richards, Kristy L.}, year={2011}, month={Jan} }
 @article{scott_sarver_gavin_thayanithy_getzy_newman_cutter_lindblad-toh_kisseberth_hunter_et al._2011, title={Molecular subtypes of osteosarcoma identified by reducing tumor heterogeneity through an interspecies comparative approach}, volume={49}, ISSN={["1873-2763"]}, DOI={10.1016/j.bone.2011.05.008}, abstractNote={The heterogeneous and chaotic nature of osteosarcoma has confounded accurate molecular classification, prognosis, and prediction for this tumor. The occurrence of spontaneous osteosarcoma is largely confined to humans and dogs. While the clinical features are remarkably similar in both species, the organization of dogs into defined breeds provides a more homogeneous genetic background that may increase the likelihood to uncover molecular subtypes for this complex disease. We thus hypothesized that molecular profiles derived from canine osteosarcoma would aid in molecular subclassification of this disease when applied to humans. To test the hypothesis, we performed genome wide gene expression profiling in a cohort of dogs with osteosarcoma, primarily from high-risk breeds. To further reduce inter-sample heterogeneity, we assessed tumor-intrinsic properties through use of an extensive panel of osteosarcoma-derived cell lines. We observed strong differential gene expression that segregated samples into two groups with differential survival probabilities. Groupings were characterized by the inversely correlated expression of genes associated with 'G2/M transition and DNA damage checkpoint' and 'microenvironment-interaction' categories. This signature was preserved in data from whole tumor samples of three independent dog osteosarcoma cohorts, with stratification into the two expected groups. Significantly, this restricted signature partially overlapped a previously defined, predictive signature for soft tissue sarcomas, and it unmasked orthologous molecular subtypes and their corresponding natural histories in five independent data sets from human patients with osteosarcoma. Our results indicate that the narrower genetic diversity of dogs can be utilized to group complex human osteosarcoma into biologically and clinically relevant molecular subtypes. This in turn may enhance prognosis and prediction, and identify relevant therapeutic targets.}, number={3}, journal={BONE}, author={Scott, Milcah C. and Sarver, Aaron L. and Gavin, Katherine J. and Thayanithy, Venugopal and Getzy, David M. and Newman, Robert A. and Cutter, Gary R. and Lindblad-Toh, Kerstin and Kisseberth, William C. and Hunter, Lawrence E. and et al.}, year={2011}, month={Sep}, pages={356–367} }
 @article{seiser_thomas_richards_kathryn kelley_moore_suter_breen_2011, title={Reading between the lines: molecular characterization of five widely used canine lymphoid tumour cell lines}, volume={11}, ISSN={1476-5810}, url={http://dx.doi.org/10.1111/j.1476-5829.2011.00299.x}, DOI={10.1111/j.1476-5829.2011.00299.x}, abstractNote={Molecular characterization of tumour cell lines is increasingly regarded as a prerequisite for defining their validity as models of in vivo neoplasia. We present the first comprehensive catalogue of genomic and transcriptional characteristics of five widely used canine lymphoid tumour cell lines. High‐resolution microarray‐based comparative genomic hybridization defined their unique profiles of genomic DNA copy number imbalance. Multicolour fluorescence in situ hybridization identified aberrant gains of MYC, KIT and FLT3 and deletions of PTEN and CDKN2 in individual cell lines, and also revealed examples of extensive structural chromosome reorganization. Gene expression profiling and RT‐PCR analyses defined the relationship between genomic imbalance and transcriptional dysregulation in each cell line, clarifying their relevance as models of discrete functional pathways with biological and therapeutic significance. In combination, these data provide an extensive resource of molecular data for directing the appropriate use of these cell lines as tools for studying canine lymphoid neoplasia.}, number={1}, journal={Veterinary and Comparative Oncology}, publisher={Wiley}, author={Seiser, E. L. and Thomas, R. and Richards, K. L. and Kathryn Kelley, M. and Moore, P. and Suter, S. E. and Breen, M.}, year={2011}, month={Nov}, pages={30–50} }
 @article{thomas_seiser_motsinger-reif_borst_valli_kelley_suter_argyle_burgess_bell_et al._2011, title={Refining tumor-associated aneuploidy through ‘genomic recoding’ of recurrent DNA copy number aberrations in 150 canine non-Hodgkin lymphomas}, volume={52}, ISSN={1042-8194 1029-2403}, url={http://dx.doi.org/10.3109/10428194.2011.559802}, DOI={10.3109/10428194.2011.559802}, abstractNote={Identification of the genomic regions most intimately associated with non-Hodgkin lymphoma (NHL) pathogenesis is confounded by the genetic heterogeneity of human populations. We hypothesize that the restricted genetic variation of purebred dogs, combined with the contrasting architecture of the human and canine karyotypes, will increase the penetrance of fundamental NHL-associated chromosomal aberrations in both species. We surveyed non-random aneuploidy in 150 canine NHL cases, revealing limited genomic instability compared to their human counterparts and no evidence for CDKN2A/B deletion in canine B-cell NHL. ‘Genomic recoding’ of canine NHL data into a ‘virtual human’ chromosome format showed remarkably few regions of copy number aberration (CNA) shared between both species, restricted to regions of dog chromosomes 13 and 31, and human chromosomes 8 and 21. Our data suggest that gene discovery in NHL may be enhanced through comparative studies exploiting the less complex association between CNAs and tumor pathogenesis in canine patients.}, number={7}, journal={Leukemia & Lymphoma}, publisher={Informa UK Limited}, author={Thomas, Rachael and Seiser, Eric L. and Motsinger-Reif, Alison and Borst, Luke and Valli, Victor E. and Kelley, Kathryn and Suter, Steven E. and Argyle, David and Burgess, Kristine and Bell, Jerold and et al.}, year={2011}, month={Mar}, pages={1321–1335} }
 @article{alföldi_di palma_grabherr_williams_kong_mauceli_russell_lowe_glor_jaffe_et al._2011, title={The genome of the green anole lizard and a comparative analysis with birds and mammals}, volume={477}, ISSN={0028-0836 1476-4687}, url={http://dx.doi.org/10.1038/nature10390}, DOI={10.1038/nature10390}, abstractNote={The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments. Among amniotes, genome sequences are available for mammals and birds, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes. Also, A. carolinensis mobile elements are very young and diverse-more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations.}, number={7366}, journal={Nature}, publisher={Springer Science and Business Media LLC}, author={Alföldi, Jessica and Di Palma, Federica and Grabherr, Manfred and Williams, Christina and Kong, Lesheng and Mauceli, Evan and Russell, Pamela and Lowe, Craig B. and Glor, Richard E. and Jaffe, Jacob D. and et al.}, year={2011}, month={Aug}, pages={587–591} }
 @article{zheng_nace_chen_watkins_sergott_homan_vandeberg_breen_stenn_2010, title={Mature Hair Follicles Generated from Dissociated Cells: A Universal Mechanism of Folliculoneogenesis}, volume={239}, ISSN={["1097-0177"]}, DOI={10.1002/dvdy.22398}, abstractNote={Abstract}, number={10}, journal={DEVELOPMENTAL DYNAMICS}, author={Zheng, Ying and Nace, Arben and Chen, Wei and Watkins, Krystal and Sergott, Luke and Homan, Ying and Vandeberg, John L. and Breen, Matthew and Stenn, Kurt}, year={2010}, month={Oct}, pages={2619–2626} }
 @article{breen_breen_williams_schultz_2010, title={Predicting Residential Air Exchange Rates from Questionnaires and Meteorology: Model Evaluation in Central North Carolina}, volume={44}, ISSN={["0013-936X"]}, DOI={10.1021/es101800k}, abstractNote={A critical aspect of air pollution exposure models is the estimation of the air exchange rate (AER) of individual homes, where people spend most of their time. The AER, which is the airflow into and out of a building, is a primary mechanism for entry of outdoor air pollutants and removal of indoor source emissions. The mechanistic Lawrence Berkeley Laboratory (LBL) AER model was linked to a leakage area model to predict AER from questionnaires and meteorology. The LBL model was also extended to include natural ventilation (LBLX). Using literature-reported parameter values, AER predictions from LBL and LBLX models were compared to data from 642 daily AER measurements across 31 detached homes in central North Carolina, with corresponding questionnaires and meteorological observations. Data was collected on seven consecutive days during each of four consecutive seasons. For the individual model-predicted and measured AER, the median absolute difference was 43% (0.17 h−1) and 40% (0.17 h−1) for the LBL and LBLX models, respectively. Additionally, a literature-reported empirical scale factor (SF) AER model was evaluated, which showed a median absolute difference of 50% (0.25 h−1). The capability of the LBL, LBLX, and SF models could help reduce the AER uncertainty in air pollution exposure models used to develop exposure metrics for health studies.}, number={24}, journal={ENVIRONMENTAL SCIENCE & TECHNOLOGY}, author={Breen, Michael S. and Breen, Miyuki and Williams, Ronald W. and Schultz, Bradley D.}, year={2010}, month={Dec}, pages={9349–9356} }
 @article{thomas_rebbeck_leroi_burt_breen_2009, title={Extensive conservation of genomic imbalances in canine transmissible venereal tumors (CTVT) detected by microarray-based CGH analysis}, volume={17}, ISSN={["1573-6849"]}, DOI={10.1007/s10577-009-9080-8}, abstractNote={Canine transmissible venereal tumor (CTVT) is an intriguing cancer that is transmitted naturally as an allograft by transplantation of viable tumor cells from affected to susceptible dogs. At least initially, the tumor is able to evade the host's immune response; thus, CTVT has potential to provide novel insights into tumor immunobiology. The nature of CTVT as a "contagious" cancer, originating from a common ancestral source of infection, has been demonstrated previously by a series of studies comparing geographically distinct tumors at the molecular level. While these studies have revealed that apparently unrelated tumors share a striking degree of karyotypic conservation, technological restraints have limited the ability to investigate the chromosome composition of CTVTs in any detail. We present characterization of a strategically selected panel of CTVT cases using microarray-based comparative genomic hybridization analysis at ~one-megabase resolution. These data show for the first time that the tumor presents with an extensive range of non-random chromosome copy number aberrations that are distributed widely throughout the dog genome. The majority of abnormalities detected were imbalances of small subchromosomal regions, often involving centromeric and telomeric sequences. All cases also showed the sex chromosome complement XO. There was remarkable conservation in the cytogenetic profiles of the tumors analyzed, with only minor variation observed between different cases. These data suggest that the CTVT genome demonstrates a vast degree of both structural and numerical reorganization that is maintained during transmission among the domestic dog population.}, number={7}, journal={CHROMOSOME RESEARCH}, author={Thomas, Rachael and Rebbeck, Clare and Leroi, Armand M. and Burt, Austin and Breen, Matthew}, year={2009}, month={Oct}, pages={927–934} }
 @article{lin_thomas_tsai_breen_london_2009, title={Generation and characterization of novel canine malignant mast cell line CL1}, volume={127}, ISSN={["1873-2534"]}, DOI={10.1016/j.vetimm.2008.09.027}, abstractNote={Studies using the currently available malignant canine mast cell lines and bone marrow-derived cultured mast cells (BMCMCs) have provided an in-depth understanding of normal and neoplastic canine mast cell biology. However, many of the currently available malignant canine mast cell lines possess limitations, including loss of cell surface markers and inability to bind canine IgE. We have recently generated a novel mast cell line, CL1, from an 11-year-old spayed female Labrador retriever diagnosed with systemic mastocytosis and neoplastic effusion. The CL1 cells express KIT, FcepsilonRI, CD44, CD45, CD14, CD11a, CD11b and CD18 as well as chymase. Interestingly, these cells express wild-type KIT, with no evidence of autophosphorylation, but are able to proliferate independently without the addition of exogenous stem cell factor (SCF), KIT ligand. However, stimulation of CL1 cells with SCF induces KIT phosphorylation promoting cell proliferation. The CL1 cells retain functional properties of mast cells, degranulating in a dose-dependent manner in response to both IgE cross-linking and chemical stimulation. Lastly, cytogenetic evaluation revealed several recurrent tumor-associated chromosome copy number imbalances in the CL1 line. In summary, the CL1 cell line possesses phenotypic and functional properties similar to those found in canine BMCMCs, and will likely be a useful tool to study mast cell biology, factors regulating transformation of mast cells, cytogenetic abnormalities in mast cell tumors, and novel preclinical therapies.}, number={1-2}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Lin, Tzu-Yin and Thomas, Rachael and Tsai, Pei-Chien and Breen, Matthew and London, Cheryl A.}, year={2009}, month={Jan}, pages={114–124} }
 @article{reitman_olby_mariani_thomas_breen_bigner_mclendon_yan_2009, title={IDH1 and IDH2 hotspot mutations are not found in canine glioma}, volume={127}, ISSN={0020-7136}, url={http://dx.doi.org/10.1002/ijc.25017}, DOI={10.1002/ijc.25017}, abstractNote={Human diffuse and anaplastic astrocytomas, well-differenti-ated and anaplastic oligodendrogliomas and secondary glio-blastomas frequently (>70%) contain somatic mutations ofthe R132 codon of the cytoplasmic NADPþ-dependent iso-citrate dehydrogenase (IDH1) or the corresponding R172codon in its homolog, IDH2.}, number={1}, journal={International Journal of Cancer}, publisher={Wiley}, author={Reitman, Zachary J. and Olby, Natasha J. and Mariani, Christopher L. and Thomas, Rachael and Breen, Matthew and Bigner, Darell D. and McLendon, Roger E. and Yan, Hai}, year={2009}, month={Oct}, pages={245–246} }
 @article{thomas_wang_tsai_langford_fosmire_jubala_getzy_cutter_modiano_breen_2009, title={Influence of genetic background on tumor karyotypes: Evidence for breed-associated cytogenetic aberrations in canine appendicular osteosarcoma}, volume={17}, ISSN={["1573-6849"]}, DOI={10.1007/s10577-009-9028-z}, abstractNote={Recurrent chromosomal aberrations in solid tumors can reveal the genetic pathways involved in the evolution of a malignancy and in some cases predict biological behavior. However, the role of individual genetic backgrounds in shaping karyotypes of sporadic tumors is unknown. The genetic structure of purebred dog breeds, coupled with their susceptibility to spontaneous cancers, provides a robust model with which to address this question. We tested the hypothesis that there is an association between breed and the distribution of genomic copy number imbalances in naturally occurring canine tumors through assessment of a cohort of Golden Retrievers and Rottweilers diagnosed with spontaneous appendicular osteosarcoma. Our findings reveal significant correlations between breed and tumor karyotypes that are independent of gender, age at diagnosis, and histological classification. These data indicate for the first time that individual genetic backgrounds, as defined by breed in dogs, influence tumor karyotypes in a cancer with extensive genomic instability.}, number={3}, journal={CHROMOSOME RESEARCH}, author={Thomas, Rachael and Wang, Huixia J. and Tsai, Pei-Chien and Langford, Cordelia F. and Fosmire, Susan P. and Jubala, Cristan M. and Getzy, David M. and Cutter, Gary R. and Modiano, Jaime F. and Breen, Matthew}, year={2009}, month={Apr}, pages={365–377} }
 @article{thomas_valli_ellis_bell_karlsson_cullen_lindblad-toh_langford_breen_2009, title={Microarray-based cytogenetic profiling reveals recurrent and subtype-associated genomic copy number aberrations in feline sarcomas}, volume={17}, ISSN={["1573-6849"]}, DOI={10.1007/s10577-009-9096-0}, abstractNote={Injection-site-associated sarcomas (ISAS), commonly arising at the site of routine vaccine administration, afflict as many as 22,000 domestic cats annually in the USA. These tumors are typically more aggressive and prone to recurrence than spontaneous sarcomas (non-ISAS), generally receiving a poorer long-term prognosis and warranting a more aggressive therapeutic approach. Although certain clinical and histological factors are highly suggestive of ISAS, timely diagnosis and optimal clinical management may be hindered by the absence of definitive markers that can distinguish between tumors with underlying injection-related etiology and their spontaneous counterpart. Specific nonrandom chromosome copy number aberrations (CNAs) have been associated with the clinical behavior of a vast spectrum of human tumors, providing an extensive resource of potential diagnostic and prognostic biomarkers. Although similar principles are now being applied with great success in other species, their relevance to feline molecular oncology has not yet been investigated in any detail. We report the construction of a genomic microarray platform for detection of recurrent CNAs in feline tumors through cytogenetic assignment of 210 large-insert DNA clones selected at intervals of approximately 15 Mb from the feline genome sequence assembly. Microarray-based profiling of 19 ISAS and 27 non-ISAS cases identified an extensive range of genomic imbalances that were highly recurrent throughout the combined panel of 46 sarcomas. Deletions of two specific regions were significantly associated with the non-ISAS phenotype. Further characterization of these regions may ultimately permit molecular distinction between ISAS and non-ISAS, as a tool for predicting tumor behavior and prognosis, as well as refining means for therapeutic intervention.}, number={8}, journal={CHROMOSOME RESEARCH}, author={Thomas, Rachael and Valli, Victor E. and Ellis, Peter and Bell, Jerold and Karlsson, Elinor K. and Cullen, John and Lindblad-Toh, Kerstin and Langford, Cordelia F. and Breen, Matthew}, year={2009}, month={Dec}, pages={987–1000} }
 @article{rebbeck_thomas_breen_leroi_burt_2009, title={ORIGINS AND EVOLUTION OF A TRANSMISSIBLE CANCER}, volume={63}, ISSN={["1558-5646"]}, DOI={10.1111/j.1558-5646.2009.00724.x}, abstractNote={Canine transmissible venereal tumor (CTVT) is an infectious disease of dogs. Remarkably, the infectious agent is the cancerous cell itself. To investigate its origin and spread, we collected 37 tumor samples from four continents and determined their evolutionary relationships using microsatellite length differences and microarray-based comparative genomic hybridization (aCGH). The different tumors show very little microsatellite variation, and the pattern of variation that does exist is consistent with a purely asexual mode of transmission. Approximately one quarter of the loci scored by aCGH show copy number variation relative to normal dogs, again with little variation among different tumor samples. Sequence analysis of the RPPH1 gene indicates an origin from either dogs or wolves, and microsatellite analysis indicates that the tumor is more than 6000 years old, and perhaps originated when dogs were first domesticated. By contrast, the common ancestor of extant tumors lived within the last few hundred years, long after the first tumor. The genetic and genomic patterns we observe are typical of those expected of asexual pathogens, and the extended time since first origin may explain the many remarkable adaptations that have enabled this mammalian cell lineage to live as a unicellular pathogen.}, number={9}, journal={EVOLUTION}, author={Rebbeck, Clare A. and Thomas, Rachael and Breen, Matthew and Leroi, Armand M. and Burt, Austin}, year={2009}, month={Sep}, pages={2340–2349} }
 @misc{breen_2009, title={Update on Genomics in Veterinary Oncology}, volume={24}, ISSN={["1946-9837"]}, DOI={10.1053/j.tcam.2009.03.002}, abstractNote={The release of an annotated human genome sequence assembly and the emergence of genomics technologies have led to significant advances in our understanding of many human diseases including cancers. As DNA sequencing technology has become less costly, the field of comparative genomics has progressed rapidly and attention has turned now to generating whole genome assemblies and dedicated genomics resources for veterinary species. Such progress brings a whole new series of opportunities to advance veterinary medicine. Many human and animal diseases share a pathogenetic basis, and although veterinary species need advances in biomedical research in their own right, the consideration of companion animals also as good comparative models for human disease saw the emergence of the "one medicine" concept. The future of many areas of human and veterinary biomedical research is very much interdependent, with one of the closest associations being in oncology. It is inevitable that veterinary oncology will benefit enormously from data derived from genomics and that this era will see a huge shift in the ways in which companion animal cancer patients are evaluated and subsequently treated. Here, we will review some of the advancements of genomics as they relate to veterinary oncology.}, number={3}, journal={TOPICS IN COMPANION ANIMAL MEDICINE}, author={Breen, Matthew}, year={2009}, month={Aug}, pages={113–121} }
 @article{thomas_duke_wang_breen_higgins_linder_ellis_langford_dickinson_olby_et al._2009, title={‘Putting our heads together’: insights into genomic conservation between human and canine intracranial tumors}, volume={94}, ISSN={0167-594X 1573-7373}, url={http://dx.doi.org/10.1007/s11060-009-9877-5}, DOI={10.1007/s11060-009-9877-5}, abstractNote={Numerous attributes render the domestic dog a highly pertinent model for cancer-associated gene discovery. We performed microarray-based comparative genomic hybridization analysis of 60 spontaneous canine intracranial tumors to examine the degree to which dog and human patients exhibit aberrations of ancestrally related chromosome regions, consistent with a shared pathogenesis. Canine gliomas and meningiomas both demonstrated chromosome copy number aberrations (CNAs) that share evolutionarily conserved synteny with those previously reported in their human counterpart. Interestingly, however, genomic imbalances orthologous to some of the hallmark aberrations of human intracranial tumors, including chromosome 22/NF2 deletions in meningiomas and chromosome 1p/19q deletions in oligodendrogliomas, were not major events in the dog. Furthermore, and perhaps most significantly, we identified highly recurrent CNAs in canine intracranial tumors for which the human orthologue has been reported previously at low frequency but which have not, thus far, been associated intimately with the pathogenesis of the tumor. The presence of orthologous CNAs in canine and human intracranial cancers is strongly suggestive of their biological significance in tumor development and/or progression. Moreover, the limited genetic heterogenity within purebred dog populations, coupled with the contrasting organization of the dog and human karyotypes, offers tremendous opportunities for refining evolutionarily conserved regions of tumor-associated genomic imbalance that may harbor novel candidate genes involved in their pathogenesis. A comparative approach to the study of canine and human intracranial tumors may therefore provide new insights into their genetic etiology, towards development of more sophisticated molecular subclassification and tailored therapies in both species.}, number={3}, journal={Journal of Neuro-Oncology}, publisher={Springer Science and Business Media LLC}, author={Thomas, Rachael and Duke, Shannon E. and Wang, Huixia J. and Breen, Tessa E. and Higgins, Robert J. and Linder, Keith E. and Ellis, Peter and Langford, Cordelia F. and Dickinson, Peter J. and Olby, Natasha J. and et al.}, year={2009}, month={Mar}, pages={333–349} }
 @article{thomas_duke_karlsson_evans_ellis_lindblad-toh_langford_breen_2008, title={A genome assembly-integrated dog 1 Mb BAC microarray: a cytogenetic resource for canine cancer studies and comparative genomic analysis}, volume={122}, ISSN={["1424-859X"]}, DOI={10.1159/000163088}, abstractNote={Molecular cytogenetic studies have been instrumental in defining the nature of numerical and structural chromosome changes in human cancers, but their significance remains to be fully understood. The emergence of high quality genome assemblies for several model organisms provides exciting opportunities to develop novel genome-integrated molecular cytogenetic resources that now permit a comparative approach to evaluating the relevance of tumor-associated chromosome aberrations, both within and between species. We have used the dog genome sequence assembly to identify a framework panel of 2,097 bacterial artificial chromosome (BAC) clones, selected at intervals of approximately one megabase. Each clone has been evaluated by multicolor fluorescence in situ hybridization (FISH) to confirm its unique cytogenetic location in concordance with its reported position in the genome assembly, providing new information on the organization of the dog genome. This panel of BAC clones also represents a powerful cytogenetic resource with numerous potential applications. We have used the clone set to develop a genome-wide microarray for comparative genomic hybridization (aCGH) analysis, and demonstrate its application in detection of tumor-associated DNA copy number aberrations (CNAs) including single copy deletions and amplifications, regional aneuploidy and whole chromosome aneuploidy. We also show how individual clones selected from the BAC panel can be used as FISH probes in direct evaluation of tumor karyotypes, to verify and explore CNAs detected using aCGH analysis. This cytogenetically validated, genome integrated BAC clone panel has enormous potential for aiding gene discovery through a comparative approach to molecular oncology.}, number={2}, journal={CYTOGENETIC AND GENOME RESEARCH}, author={Thomas, R. and Duke, S. E. and Karlsson, E. K. and Evans, A. and Ellis, P. and Lindblad-Toh, K. and Langford, C. F. and Breen, M.}, year={2008}, pages={110–121} }
 @article{breen_2008, title={Canine cytogenetics - from band to basepair}, volume={120}, ISSN={["1424-859X"]}, DOI={10.1159/000118740}, abstractNote={Humans and dogs have coexisted for thousands of years, during which time we have developed a unique bond, centered on companionship. Along the way, we have developed purebred dog breeds in a manner that has resulted unfortunately in many of them being affected by serious genetic disorders, including cancers. With serendipity and irony the unique genetic architecture of the 21st century genome of Man’s best friend may ultimately provide many of the keys to unlock some of nature’s most intriguing biological puzzles. Canine cytogenetics has advanced significantly over the past 10 years, spurred on largely by the surge of interest in the dog as a biomedical model for genetic disease and the availability of advanced genomics resources. As such the role of canine cytogenetics has moved rapidly from one that served initially to define the gross genomic organization of the canine genome and provide a reliable means to determine the chromosomal location of individual genes, to one that enabled the assembled sequence of the canine genome to be anchored to the karyotype. Canine cytogenetics now presents the biomedical research community with a means to assist in our search for a greater understanding of how genome architectures altered during speciation and in our search for genes associated with cancers that affect both dogs and humans. The cytogenetics ‘toolbox’ for the dog is now loaded. This review aims to provide a summary of some of the recent advancements in canine cytogenetics.}, number={1-2}, journal={CYTOGENETIC AND GENOME RESEARCH}, author={Breen, M.}, year={2008}, pages={50–60} }
 @article{zaunbrecher_mir_dunne_breen_piedrahita_2008, title={Enhancement of extra chromosomal recombination in somatic cells by affecting the ratio of homologous recombination (HR) to non-homologous end joining (NHEJ)}, volume={19}, ISSN={["1532-2378"]}, DOI={10.1080/10495390701670099}, abstractNote={Advancements in somatic cell gene targeting have been slow due to the finite lifespan of somatic cells and the overall inefficiency of homologous recombination. The rate of homologous recombination is determined by mechanisms of DNA repair, and by the balance between homologous recombination (HR) and non-homologous end joining (NHEJ). A plasmid-to-plasmid, extra chromosomal recombination system was used to study the effects of the manipulation of molecules involved in NHEJ (Mre11, Ku70/80, and p53) on HR/NHEJ ratios. In addition, the effect of telomerase expression, cell synchrony, and DNA nuclear delivery was examined. While a mutant Mre11 and an anti-Ku aptamer did not significantly affect the rate of NHEJ or HR, transient expression of a p53 mutant increased overall HR/NHEJ by 2.5 fold. However, expression of the mutant p53 resulted in increased aneuploidy of the cultured cells. Additionally, we found no relationship between telomerase expression and changes in HR/NHEJ. In contrast, cell synchrony by thymidine incorporation did not induce chromosomal abnormalities, and increased the ratio of HR/NHEJ 5-fold by reducing the overall rate of NHEJ. Overall our results show that attempts at reducing NHEJ by use of Mre11 or anti-Ku aptamers were unsuccessful. Cell synchrony via thymidine incorporation, however, does increase the ratio of HR/NHEJ and this indicates that this approach may be of use to facilitate targeting in somatic cells by reducing the numbers of colonies that need to be analyzed before a HR is identified.}, number={1}, journal={ANIMAL BIOTECHNOLOGY}, author={Zaunbrecher, Gretchen M. and Mir, Bashir and Dunne, Patrick W. and Breen, Matthew and Piedrahita, Jorge A.}, year={2008}, pages={6–21} }
 @article{breen_modiano_2008, title={Evolutionarily conserved cytogenetic changes in hematological malignancies of dogs and humans - man and his best friend share more than companionship}, volume={16}, ISSN={["1573-6849"]}, DOI={10.1007/s10577-007-1212-4}, abstractNote={The pathophysiological similarities shared by many forms of human and canine disease, combined with the sophisticated genomic resources now available for the dog, have placed 'man's best friend' in a position of high visibility as a model system for a variety of biomedical concerns, including cancer. The importance of nonrandom cytogenetic abnormalities in human leukemia and lymphoma was recognized over 40 years ago, but the mechanisms of genome reorganization remain incompletely understood. The development of molecular cytogenetics, using fluorescence in situ hybridization (FISH) technology, has played a significant role in our understanding of cancer biology by providing a means for 'interrogating' tumor cells for a variety of gross genetic changes in the form of either numerical or structural chromosome aberrations. Here, we have identified cytogenetic abnormalities in naturally occurring canine hematopoietic tumors that are evolutionarily conserved compared with those that are considered characteristic of the corresponding human condition. These data suggest that humans and dogs share an ancestrally retained pathogenetic basis for cancer and that cytogenetic evaluation of canine tumors may provide greater insight into the biology of tumorigenesis.}, number={1}, journal={CHROMOSOME RESEARCH}, author={Breen, Matthew and Modiano, Jaime F.}, year={2008}, month={Mar}, pages={145–154} }
 @article{young_kirkness_breen_2008, title={Tackling the characterization of canine chromosomal breakpoints with an integrated in-situ/in-silico approach: The canine PAR and PAB}, volume={16}, ISSN={["1573-6849"]}, DOI={10.1007/s10577-008-1268-9}, abstractNote={The domestic dog continues to represent an influential model organism for comparative biomedical research owing to the numerous genetic and pathophysiological similarities shared between human and dog diseases. The combined availability of a high-quality genome assembly and a 1 Mb-resolution genome-assembly integrated bacterial artificial chromosome (BAC) panel now provides the essential resources to combine cytogenetic and computational analyses to determine the precise locations of chromosome breakpoint regions within aberrant karyotypes. In this study we demonstrate the synergy of using a such a combined in-situ/in-silico approach to define chromosome breakpoints using the naturally occurring breakpoint present on all canine X chromosomes--the pseudoautosomal breakpoint (PAB). In so doing we have further characterized the canine pseudoautosomal region (PAR) to extend approximately 6.6 Mb from the telomeric end of CFA Xp and established that the canine PAB is contained within a 2 kb region. Our characterization of the canine PAR allowed for the comparative study of gene content across previously defined mammalian PARs and indicates that the canine PAB is contained with the gene Shroom2. The future application of the approach demonstrated in this study will prove useful when seeking to identify the genomic sequences surrounding recurrent chromosome breakpoints present in canine cancers.}, number={8}, journal={CHROMOSOME RESEARCH}, author={Young, Andrea C. and Kirkness, Ewen F. and Breen, Matthew}, year={2008}, month={Dec}, pages={1193–1202} }
 @article{thomas_duke_bloom_breen_young_feiste_seiser_tsai_langford_ellis_et al._2007, title={A cytogenetically characterized, genome-anchored 10-Mb BAC set and CGH array for the domestic dog}, volume={98}, ISSN={["0022-1503"]}, DOI={10.1093/jhered/esm053}, abstractNote={The generation of a 7.5x dog genome assembly provides exciting new opportunities to interpret tumor-associated chromosome aberrations at the biological level. We present a genomic microarray for array comparative genomic hybridization (aCGH) analysis in the dog, comprising 275 bacterial artificial chromosome (BAC) clones spaced at intervals of approximately 10 Mb. Each clone has been positioned accurately within the genome assembly and assigned to a unique chromosome location by fluorescence in situ hybridization (FISH) analysis, both individually and as chromosome-specific BAC pools. The microarray also contains clones representing the dog orthologues of 31 genes implicated in human cancers. FISH analysis of the 10-Mb BAC clone set indicated excellent coverage of each dog chromosome by the genome assembly. The order of clones was consistent with the assembly, but the cytogenetic intervals between clones were variable. We demonstrate the application of the BAC array for aCGH analysis to identify both whole and partial chromosome imbalances using a canine histiocytic sarcoma case. Using BAC clones selected from the array as probes, multicolor FISH analysis was used to further characterize these imbalances, revealing numerous structural chromosome rearrangements. We outline the value of a combined aCGH/FISH approach, together with a well-annotated dog genome assembly, in canine and comparative cancer studies.}, number={5}, journal={JOURNAL OF HEREDITY}, author={Thomas, Rachael and Duke, Shannon E. and Bloom, Stephanie K. and Breen, Tessa E. and Young, Andrea C. and Feiste, Erika and Seiser, Eric L. and Tsai, Pei-Chien and Langford, Cordelia F. and Ellis, Peter and et al.}, year={2007}, pages={474–484} }
 @article{kisseberth_nadella_breen_thomas_duke_murahari_kosarek_vernau_avery_burkhard_et al._2007, title={A novel canine lymphoma cell line: A translational and comparative model for lymphoma research}, volume={31}, ISSN={["1873-5835"]}, DOI={10.1016/j.leukres.2007.04.003}, abstractNote={A novel canine lymphoma cell line, OSW, was established from the malignant pleural effusion of a dog with peripheral T-cell lymphoma. The immunoprofile as determined by flow cytometry was as follows: positive for CD45, CD49d, CD18, CD11a; weakly positive for CD11b, CD11c, CD11d; and negative for CD45RA, CD1a, CD1c, CD3, TCRalphabeta, TCRgammadelta, CD4, CD5, CD8a, CD8b, CD90(Thy1), CD21, MHCII, CD14(TUK4), CD34, and MPO. Immunocytochemistry of cytospin preparations was negative for cytoplasmic CD3, CD79a, and MPO, but was positive for CD20. The cell line had an oligoclonal T-cell receptor gamma (TCRgamma) gene rearrangement. Array comparative genomic hybridization (aCGH) and single locus probe (SLP) analysis showed that there were copy number increases of loci on dog chromosome 13 (CFA 13), and copy number decreases were evident for regions of CFA 11, 22, 26, 30 and 32, which include several of the more common chromosomal aberrations reported previously in canine lymphoma. The OSW cell line grows rapidly in vitro and is tumorigenic as a xenograft in SCID/NOD mice. OSW represents one of only a few reported canine lymphoma cell lines and is the most thoroughly characterized. This cell line and xenograft represent significant in vitro and in vivo models, respectively, for comparative and translational lymphoma research.}, number={12}, journal={LEUKEMIA RESEARCH}, author={Kisseberth, William C. and Nadella, Murali Vara Prasad and Breen, Matthew and Thomas, Rachael and Duke, Shannon E. and Murahari, Sridhar and Kosarek, Carrie E. and Vernau, William and Avery, Anne C. and Burkhard, Mary Jo and et al.}, year={2007}, month={Dec}, pages={1709–1720} }
 @misc{mikkelsen_wakefield_aken_amemiya_chang_duke_garber_gentles_goodstadt_heger_et al._2007, title={Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences}, volume={447}, ISSN={["1476-4687"]}, DOI={10.1038/nature05805}, abstractNote={We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.}, number={7141}, journal={NATURE}, author={Mikkelsen, Tarjei S. and Wakefield, Matthew J. and Aken, Bronwen and Amemiya, Chris T. and Chang, Jean L. and Duke, Shannon and Garber, Manuel and Gentles, Andrew J. and Goodstadt, Leo and Heger, Andreas and et al.}, year={2007}, month={May}, pages={167–U1} }
 @article{fosmire_thomas_jubala_wojcieszyn_valli_getzy_smith_gardner_ritt_bell_et al._2007, title={Inactivation of the p16 cyclin-dependent kinase inhibitor in high-grade canine non-Hodgkin's T-Cell lymphoma}, volume={44}, ISSN={["1544-2217"]}, DOI={10.1354/vp.44-4-467}, abstractNote={ The significance of p16/Rb tumor suppressor pathway inactivation in T-cell non-Hodgkin's lymphoma (NHL) remains incompletely understood. We used naturally occurring canine NHL to test the hypothesis that p16 inactivation has specific pathologic correlates. Forty-eight samples (22 T-cell NHL and 26 B-cell NHL) were included. As applicable, metaphase- or array-based comparative genomic hybridization, Southern blotting, promoter methylation, and Rb phosphorylation were used to determine the presence, expression, and activity of p16. Fisher's exact test was used to test for significance. Deletion of p16 (or loss of dog chromosome 11) was restricted to high-grade T-cell NHL (lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified). These were characterized by a concomitant increase of tumor cells with Rb phosphorylation at canonical CDK4 sites. Rb phosphorylation also was seen in high-grade B-cell NHL (diffuse large B-cell lymphoma and Burkitt-type lymphoma), but in those cases, it appeared to be associated with c-Myc overexpression. The data show that p16 deletion or inactivation occurs almost exclusively in high-grade T-cell NHL; however, alternative pathways can generate functional phenotypes of Rb deficiency in low-grade T-cell NHL and in high-grade B-cell NHL. Both morphologic classification according to World Health Organization criteria and assessment of Rb phosphorylation are prognostically valuable parameters for canine NHL. }, number={4}, journal={VETERINARY PATHOLOGY}, author={Fosmire, S. P. and Thomas, R. and Jubala, C. M. and Wojcieszyn, J. W. and Valli, V. E. O. and Getzy, D. M. and Smith, T. L. and Gardner, L. A. and Ritt, M. G. and Bell, J. S. and et al.}, year={2007}, month={Jul}, pages={467–478} }
 @article{duke_samollow_mauceli_lindblad-toh_breen_2007, title={Integrated cytogenetic BAC map of the genome of the gray, short-tailed opossum, Monodelphis domestica}, volume={15}, ISSN={["1573-6849"]}, DOI={10.1007/s10577-007-1131-4}, abstractNote={The generation of high-quality genome assemblies for numerous species is advancing at a rapid pace. As the number of genome assemblies increases, so does our ability to investigate genome relationships and their contributions to unraveling complex biological, evolutionary, and biomedical processes. A key process in the generation of a genome assembly is to determine and verify the precise physical location and order of the large sequence blocks (scaffolds) that result from the assembly. For organisms of relatively recent common ancestry this process may be achieved largely through comparative sequence alignment. However, as the evolutionary distance between species lengthens, the use of comparative sequence alignment becomes increasingly less reliable. Simultaneous cytogenetic mapping, using multicolor fluorescence in-situ hybridization (FISH) analysis, offers an alternative means to define the cytogenetic location and relative order of DNA sequences, thereby anchoring the genome sequence to the karyotype. In this article we report the molecular cytogenetic locations of 415 bacterial artificial chromosome (BAC) clones that served to anchor sequence scaffolds of the gray, short-tailed opossum (Monodelphis domestica) to its karyotype, which enabled accurate integration of these regions into the genome assembly.}, number={3}, journal={CHROMOSOME RESEARCH}, author={Duke, S. E. and Samollow, P. B. and Mauceli, E. and Lindblad-Toh, K. and Breen, M.}, year={2007}, month={Apr}, pages={361–370} }
 @article{modiano_breen_valli_wojcieszyn_cutter_2007, title={Predictive value of p16 or Rb inactivation in a model of naturally occurring canine non-Hodgkin's lymphoma}, volume={21}, ISSN={0887-6924 1476-5551}, url={http://dx.doi.org/10.1038/sj.leu.2404392}, DOI={10.1038/sj.leu.2404392}, number={1}, journal={Leukemia}, publisher={Springer Science and Business Media LLC}, author={Modiano, J F and Breen, M and Valli, V E O and Wojcieszyn, J W and Cutter, G R}, year={2007}, pages={184–187} }
 @article{davidow_breen_duke_samollow_mccarrey_lee_2007, title={The search for a marsupial XIC reveals a break with vertebrate synteny}, volume={15}, ISSN={1573-6849}, url={http://dx.doi.org/10.1007/s10577-007-1121-6}, DOI={10.1007/s10577-007-1121-6}, abstractNote={X-chromosome inactivation (XCI) evolved in mammals to deal with X-chromosome dosage imbalance between the XX female and the XY male. In eutherian mammals, random XCI of the soma requires a master regulatory locus known as the 'X-inactivation center' (XIC/Xic), wherein lies the noncoding XIST/Xist silencer RNA and its regulatory antisense Tsix gene. By contrast, marsupial XCI is imprinted to occur on the paternal X chromosome. To determine whether marsupials and eutherians share the XIC-driven mechanism, we search for the sequence equivalents in the genome of the South American opossum, Monodelphis domestica. Positional cloning and bioinformatic analysis reveal several interesting findings. First, protein-coding genes that flank the eutherian XIC are well-conserved in M. domestica, as well as in chicken, frog, and pufferfish. However, in M. domestica we fail to identify any recognizable XIST or TSIX equivalents. Moreover, cytogenetic mapping shows a surprising break in synteny with eutherian mammals and other vertebrates. Therefore, during the evolution of the marsupial X chromosome, one or more rearrangements broke up an otherwise evolutionarily conserved block of vertebrate genes. The failure to find XIST/TSIX in M. domestica may suggest that the ancestral XIC is too divergent to allow for detection by current methods. Alternatively, the XIC may have arisen relatively late in mammalian evolution, possibly in eutherians with the emergence of random XCI. The latter argues that marsupial XCI does not require XIST and opens the search for alternative mechanisms of dosage compensation.}, number={2}, journal={Chromosome Research}, publisher={Springer Science and Business Media LLC}, author={Davidow, Lance S. and Breen, Matthew and Duke, Shannon E. and Samollow, Paul B. and McCarrey, John R. and Lee, Jeannie T.}, year={2007}, month={Feb}, pages={137–146} }
 @misc{khanna_lindblad-toh_vail_london_bergman_barber_breen_kitchell_mcneil_modiano_et al._2006, title={The dog as a cancer model}, volume={24}, ISSN={["1087-0156"]}, DOI={10.1038/nbt0906-1065b}, number={9}, journal={NATURE BIOTECHNOLOGY}, author={Khanna, Chand and Lindblad-Toh, Kerstin and Vail, David and London, Cheryl and Bergman, Philip and Barber, Lisa and Breen, Matthew and Kitchell, Barbara and McNeil, Elizabeth and Modiano, Jaime F. and et al.}, year={2006}, month={Sep}, pages={1065–1066} }
 @article{lindblad-toh_wade_mikkelsen_karlsson_jaffe_kamal_clamp_chang_kulbokas_zody_et al._2005, title={Genome sequence, comparative analysis and haplotype structure of the domestic dog}, volume={438}, ISSN={0028-0836 1476-4687}, url={http://dx.doi.org/10.1038/nature04338}, DOI={10.1038/nature04338}, abstractNote={Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.}, number={7069}, journal={Nature}, publisher={Springer Science and Business Media LLC}, author={Lindblad-Toh, Kerstin and Wade, Claire M and Mikkelsen, Tarjei S. and Karlsson, Elinor K. and Jaffe, David B. and Kamal, Michael and Clamp, Michele and Chang, Jean L. and Kulbokas, Edward J., III and Zody, Michael C. and et al.}, year={2005}, month={Dec}, pages={803–819} }
 @article{comstock_lingaas_kirkness_hitte_thomas_breen_galibert_ostrander_2004, title={A high-resolution comparative map of canine Chromosome 5q14.3–q33 constructed utilizing the 1.5× canine genomesequence}, volume={15}, ISSN={0938-8990 1432-1777}, url={http://dx.doi.org/10.1007/s00335-004-2365-5}, DOI={10.1007/s00335-004-2365-5}, abstractNote={A high-density map of the region of canine Chromosome 5 (CFA5) surrounding the evolutionary breakpoint between human Chromosomes 1p32 and 17pll was constructed by integrating a radiation hybrid map including 41 microsatellites, 10 BACs, and 59 genes and a linkage map including 18 markers. A collection of canine genomic survey sequences providing 1.5x coverage was used to identify dog orthologs of human genes, proving instrumental in the development of this map. Of particular interest is the canine BHD gene, within which we have previously described a single nucleotide polymorphism associated with Hereditary Multifocal Renal Cystadenocarcinoma and Nodular Dermatofibrosis (RCND) in German Shepherd dogs. The corresponding region of the human genome is particularly gene rich, containing genes involved in development, metabolism, and cancer that are likely to be of interest in future mapping studies. This current mapping effort on CFA5 expands the degree to which initial findings of linkage in canine families can be followed by successful positional cloning efforts and increases the value of the human genome sequence for defining candidate genes. Moreover, this study demonstrates the utility of genomic survey sequences when combined with accurate genome maps for rapid mapping of disease susceptibility loci.}, number={7}, journal={Mammalian Genome}, publisher={Springer Science and Business Media LLC}, author={Comstock, KenineE. and Lingaas, Frode and Kirkness, EwenF. and Hitte, Christophe and Thomas, Rachael and Breen, Matthew and Galibert, Francis and Ostrander, ElaineA.}, year={2004}, month={Jul}, pages={544–551} }
 @article{fosmire_dickerson_scott_bianco_pettengill_meylemans_padilla_frazer-abel_akhtar_getzy_et al._2004, title={Canine malignant hemangiosarcoma as a model of primitive angiogenic endothelium}, volume={84}, ISSN={0023-6837 1530-0307}, url={http://dx.doi.org/10.1038/labinvest.3700080}, DOI={10.1038/labinvest.3700080}, abstractNote={Hemangiosarcoma (HSA) is a common untreatable cancer of dogs that resembles human angiosarcoma. Detailed studies of these diseases have been historically hindered by the paucity of suitable reagents. Here, we show that expression of CD117 (c-Kit) can distinguish primitive (malignant) from mature (benign) proliferative endothelial lesions, and we describe eight independent cell lines derived from canine HSA explants. Endothelial origin was confirmed by sustained expression of surface CD105 (endoglin), CD146 (MUC18), and CD51/CD61 (alpha(v)beta(3) integrin). The cell lines showed anchorage-independent growth and were motile and invasive when cultured on a basement membrane matrix. They required endothelial growth factors for growth and survival, and they could be induced to form tubular structures resembling blood vessels when cultured under low calcium conditions. The formation of vessel-like structures was blocked by nicotine, and restored by FK506, suggesting that 'nuclear factor of activated T cells' activity prevents differentiation of these cells. In summary, these cell lines represent a unique and novel resource to improve our understanding of endothelial cell biology in general and canine HSA in particular.}, number={5}, journal={Laboratory Investigation}, publisher={Springer Science and Business Media LLC}, author={Fosmire, Susan P and Dickerson, Erin B and Scott, Allyson M and Bianco, Stacie R and Pettengill, Marilyn J and Meylemans, Heather and Padilla, Marcia and Frazer-Abel, Ashley A and Akhtar, Nasim and Getzy, David M and et al.}, year={2004}, month={Apr}, pages={562–572} }
 @article{palkopoulou_lipson_mallick_nielsen_rohland_baleka_karpinski_ivancevici_to_kortschak_et al., title={A comprehensive genomic history of extinct and living elephants}, volume={115}, number={11}, journal={Proceedings of the National Academy of Sciences of the United States of America}, author={Palkopoulou, E. and Lipson, M. and Mallick, S. and Nielsen, S. and Rohland, N. and Baleka, S. and Karpinski, E. and Ivancevici, A. M. and To, T. H. and Kortschak, D. and et al.}, pages={E2566–2574} }
 @article{leblanc_mazcko_brown_koehler_miller_miller_bentley_packer_breen_boudreau_et al., title={Creation of an NCI comparative brain tumor consortium: informing the translation of new knowledge from canine to human brain tumor patients}, volume={18}, number={9}, journal={Neuro-oncology}, author={LeBlanc, A. K. and Mazcko, C. and Brown, D. E. and Koehler, J. W. and Miller, A. D. and Miller, C. R. and Bentley, R. T. and Packer, R. A. and Breen, M. and Boudreau, C. E. and et al.}, pages={1209–1218} }
 @article{duke_samallow_mauceli_lindblad-toh_breen, title={Cytogenetic BAC map of the genome of Monodelphis domestica}, volume={15}, journal={Chromosome Research}, author={Duke, S. E. and Samallow, P. and Mauceli, E. and Lindblad-Toh, K. and Breen, M.}, pages={3610–3670} }
 @article{elvers_turner-maier_swofford_koltookian_johnson_stewart_zhang_schumacher_beroukhim_rosenberg_et al., title={Exome sequencing of lymphomas from three dog breeds reveals somatic mutation patterns reflecting genetic background}, volume={25}, number={11}, journal={Genome Research}, author={Elvers, I. and Turner-Maier, J. and Swofford, R. and Koltookian, M. and Johnson, J. and Stewart, C. and Zhang, C. Z. and Schumacher, S. E. and Beroukhim, R. and Rosenberg, M. and et al.}, pages={1634–1645} }
 @misc{mikkelsen_wakefield_aken_amemiya_chang_duke_garber_gentles_goodstadt_heger_et al., title={Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences}, volume={447}, number={7141}, journal={254}, author={Mikkelsen, T. S. and Wakefield, M. J. and Aken, B. and Amemiya, C. T. and Chang, J. L. and Duke, S. and Garber, M. and Gentles, A. J. and Goodstadt, L. and Heger, A. and et al.}, pages={167–1} }
 @article{karlsson_sigurdsson_ivansson_thomas_elvers_wright_howald_tonomura_perloski_swofford_et al., title={Genome-wide analyses implicate 33 loci in heritable dog osteosarcoma, including regulatory variants near CDKN2A/B}, volume={14}, number={12}, journal={Genome Biology}, author={Karlsson, E. K. and Sigurdsson, S. and Ivansson, E. and Thomas, R. and Elvers, I. and Wright, J. and Howald, C. and Tonomura, N. and Perloski, M. and Swofford, R. and et al.} }
 @article{tonomura_elvers_thomas_megquier_turner-maier_howald_sarver_swofford_frantz_ito_et al., title={Genome-wide association study identifies shared risk loci common to two malignancies in golden retrievers}, volume={11}, number={2}, journal={PLoS Genetics}, author={Tonomura, N. and Elvers, I. and Thomas, R. and Megquier, K. and Turner-Maier, J. and Howald, C. and Sarver, A. L. and Swofford, R. and Frantz, A. M. and Ito, D. and et al.} }
 @article{frantz_sarver_ito_phang_karimpour-fard_scott_valli_lindblad-toh_burgess_husbands_et al., title={Molecular profiling reveals prognostically significant subtypes of canine lymphoma}, volume={50}, number={4}, journal={Veterinary Pathology}, author={Frantz, A. M. and Sarver, A. L. and Ito, D. and Phang, T. L. and Karimpour-Fard, A. and Scott, M. C. and Valli, V. E. O. and Lindblad-Toh, K. and Burgess, K. E. and Husbands, B. D. and et al.}, pages={693–703} }
 @article{modiano_breen_lana_ehrhart_fosmire_thomas_jubala_lamerato-kozicki_ehrhart_schaack_et al., title={Naturally occurring translational models for development of cancer gene therapy}, volume={10A}, journal={Gene Therapy & Molecular Biology}, author={Modiano, J. F. and Breen, M. and Lana, S. E. and Ehrhart, N. and Fosmire, S. P. and Thomas, R. and Jubala, C. M. and Lamerato-Kozicki, A. R. and Ehrhart, E. J. and Schaack, J. and et al.}, pages={31–40} }
 @article{leblanc_breen_choyke_dewhirst_fan_gustafson_helman_kastan_knapp_levin_et al., title={Perspectives from man's best friend: National Academy of Medicine's Workshop on Comparative Oncology}, volume={8}, number={324}, journal={Science Translational Medicine}, author={LeBlanc, A. K. and Breen, M. and Choyke, P. and Dewhirst, M. and Fan, T. M. and Gustafson, D. L. and Helman, L. J. and Kastan, M. B. and Knapp, D. W. and Levin, W. J. and et al.} }
 @misc{modiano_breen_o valli_wojcieszyn_cutter, title={Predictive value of p16 or Rb inactivation in a model of naturally occurring canine non-Hodgkin's lymphoma}, volume={21}, number={1}, journal={Leukemia}, author={Modiano, J. F. and Breen, M. and O Valli, V. E. and Wojcieszyn, J. W. and Cutter, G. R.}, pages={184–187} }
 @article{sakthikumar_elvers_kim_arendt_thomas_turner-maier_swofford_johnson_schumacher_alfoldi_et al., title={SETD2 is recurrently mutated in whole-exome sequenced canine osteosarcoma}, volume={78}, number={13}, journal={Cancer Research}, author={Sakthikumar, S. and Elvers, I. and Kim, J. and Arendt, M. L. and Thomas, R. and Turner-Maier, J. and Swofford, R. and Johnson, J. and Schumacher, S. E. and Alfoldi, J. and et al.}, pages={3421–3431} }
 @article{borgatti_koopmeiners_sarver_winter_stuebner_todhunter_rizzardi_henriksen_schmechel_forster_et al., title={Safe and effective sarcoma therapy through bispecific targeting of EGFR and uPAR}, volume={16}, number={5}, journal={Molecular Cancer Therapeutics}, author={Borgatti, A. and Koopmeiners, J. S. and Sarver, A. L. and Winter, A. L. and Stuebner, K. and Todhunter, D. and Rizzardi, A. E. and Henriksen, J. C. and Schmechel, S. and Forster, C. L. and et al.}, pages={956–965} }
 @article{shearin_hedan_cadieu_erich_schmidt_faden_cullen_abadie_kwon_grone_et al., title={The MTAP-CDKN2A locus confers susceptibility to a naturally occurring canine cancer}, volume={21}, number={7}, journal={Cancer Epidemiology Biomarkers}, author={Shearin, A. L. and Hedan, B. and Cadieu, E. and Erich, S. A. and Schmidt, E. V. and Faden, D. L. and Cullen, J. and Abadie, J. and Kwon, E. M. and Grone, A. and et al.}, pages={1019–1027} }
 @article{alfoldi_di palma_grabherr_williams_kong_mauceli_russell_lowe_glor_jaffe_et al., title={The genome of the green anole lizard and a comparative analysis with birds and mammals}, volume={477}, number={7366}, journal={Nature}, author={Alfoldi, J. and Di Palma, F. and Grabherr, M. and Williams, C. and Kong, L. S. and Mauceli, E. and Russell, P. and Lowe, C. B. and Glor, R. E. and Jaffe, J. D. and et al.}, pages={587–591} }
 @article{green_braun_armstrong_earl_nguyen_hickey_vandewege_st john_capella-gutierrez_castoe_et al., title={Three crocodilian genomes reveal ancestral patterns of evolution among archosaurs}, volume={346}, number={6215}, journal={Science}, author={Green, R. E. and Braun, E. L. and Armstrong, J. and Earl, D. and Nguyen, N. and Hickey, G. and Vandewege, M. W. and St John, J. A. and Capella-Gutierrez, S. and Castoe, T. A. and et al.}, pages={1335-} }