Comparative Molecular Life History of Spontaneous Canine and Human Gliomas

Amin, Samir B.; Anderson, Kevin J.; Boudreau, C. Elizabeth; Martinez-Ledesma, Emmanuel; Kocakavuk, Emre; Johnson, Kevin C.; Barthel, Floris P.; Varn, Frederick S.; Kassab, Cynthia; Ling, Xiaoyang; Kim, Hoon; Barter, Mary; Lau, Ching C.; Ngan, Chew Yee; Chapman, M. John; Koehler, Jey W.; Long, James P.; Miller, Andrew D.; Miller, C. Ryan; Porter, Brian F.; Rissi, Daniel R.; Mazcko, Christina; LeBlanc, Amy K.; Dickinson, Peter J.; Packer, Rebecca A.; Taylor, Amanda R.; Rossmeisl, John H.; Woolard, Kevin D.; Heimberger, Amy B.; Levine, Jonathan M.; Verhaak, Roel G.W.

doi:10.1016/j.ccell.2020.01.004

Cited by 60 publications

(104 citation statements)

References 104 publications

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“…We performed a rigorous quality control (QC) on the WES data published for 601 canine cases. The 601 canine cases consist of over six cancer types, including mammary cancer 13 , oral melanoma 11 , osteosarcoma 15 , lymphoma 16 , glioma 12 and hemangiosarcoma 17 (Table S1). They represent over 35 breeds (Table S1A).…”

Section: Resultsmentioning

confidence: 99%

“…They represent over 35 breeds (Table S1A). Their WES data were generated by different groups, using different exome-capturing kits and Illumina sequencing machines [11][12][13][15][16][17] . We hence performed a rigorous QC to ensure that each study met a set of quality standards before any further integrative analysis.…”

Section: Resultsmentioning

confidence: 99%

“…Among these cancers, the mammary cancer study 13 has the most comprehensive case information provided in the SRA database and related publications [11][12][13][15][16][17] (Table S1). It has not only the patient info (e.g., age, sex, breed), but also histological subtypes and limited clinic data (e.g., tumor invasiveness, patient alive/death status).…”

Section: Resultsmentioning

confidence: 99%

“…Do the same hold true for canine cancers? A recent study reports similar mutation rates for mucosal melanoma between the two species 11 , while another study reports that canine and pediatric glioma are closer in mutation rate than canine and adult glioma 12 .…”

Section: Introductionmentioning

confidence: 94%

“…To answer these questions, we performed a pan-cancer and pan-breed study with 710 canine cases with public whole exome sequencing (WES) and/or whole genome sequencing (WGS) data [11][12][13][14][15][16][17][18][19][20][21][22] . We used 601 cases with WES data [11][12][13][15][16][17] for discovery, and 18 with WES data 18,23 and 91 with WGS data [18][19][20][21][22] for validation. We also compared our canine findings to those published for the corresponding human cancers 3,4,[24][25][26][27] .…”

Section: Introductionmentioning

confidence: 99%

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Canine tumor mutation rate is positively correlated with TP53 mutation across cancer types and breeds

Alsaihati

Watson

et al. 2020

Preprint

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Spontaneous canine cancers are a valuable but relatively understudied and underutilized model in cancer research. To enhance their usage, we reanalyzed whole exome sequencing data published for 601 dogs with mammary cancer, osteosarcoma, oral melanoma, lymphoma, glioma or hemangiosarcoma from over 35 breeds, after rigorous quality control, including breed validation. Each cancer type harbors distinct molecular features, with major pathway alterations matching its human counterpart (e.g., PI3K for mammary cancer and p53 for osteosarcoma). On average, mammary cancer and glioma have lower mutation rates (median <0.5 mutation per Mb), whereas oral melanoma, osteosarcoma and hemangiosarcoma have higher mutation rates (median ≥1 mutation per Mb). Across cancer types and across breeds, the mutation rate is strongly associated with TP53 mutation, but not with PIK3CA mutation. The mutation rate is also associated with a mutation signature enriched in osteosarcoma of Golden Retrievers, independent of TP53 mutation. Finally, compared to other breeds examined, DNA repair genes appear to be less conserved in Golden Retriever which is predisposed to numerous cancers.

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