Canine tumor mutational burden is correlated with TP53 mutation across tumor types and breeds

被引：39

作者：

Alsaihati, Burair A. ^{[1
,2
]}

Ho, Kun-Lin ^{[1
]}

Watson, Joshua ^{[1
]}

Feng, Yuan ^{[1
]}

Wang, Tianfang ^{[1
]}

Dobbin, Kevin K. ^{[3
]}

Zhao, Shaying ^{[1
]}

机构：

[1] Univ Georgia, Inst Bioinformat, Dept Biochem & Mol Biol, Athens, GA 30602 USA

[2] King Abdulaziz City Sci & Technol, Natl Ctr Genom Technol, Riyadh, Saudi Arabia

[3] Univ Georgia, Dept Epidemiol & Biostat, Athens, GA 30602 USA

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

关键词：

GENOMIC LANDSCAPE; SOMATIC MUTATION; CANCER GENOME; DISCOVERY; SEQUENCE; DNA; SIGNATURES; GLIOMA; DOG;

D O I：

10.1038/s41467-021-24836-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Spontaneous canine cancers are valuable but relatively understudied and underutilized models. To enhance their usage, we reanalyze whole exome and genome sequencing data published for 684 cases of >7 common tumor types and >35 breeds, with rigorous quality control and breed validation. Our results indicate that canine tumor alteration landscape is tumor type-dependent, but likely breed-independent. Each tumor type harbors major pathway alterations also found in its human counterpart (e.g., PI3K in mammary tumor and p53 in osteosarcoma). Mammary tumor and glioma have lower tumor mutational burden (TMB) (median<0.5 mutations per Mb), whereas oral melanoma, osteosarcoma and hemangiosarcoma have higher TMB (median >= 1 mutations per Mb). Across tumor types and breeds, TMB is associated with mutation of TP53 but not PIK3CA, the most mutated genes. Golden Retrievers harbor a TMB-associated and osteosarcoma-enriched mutation signature. Here, we provide a snapshot of canine mutations across major tumor types and breeds.

引用

页数：13