Department of Biochemistry and Molecular Biology, Institute of Bioinformatics, University of Georgia, Athens, GA, USA.
National Center for Genomics Technology, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
Nat Commun. 2021 Aug 3;12(1):4670. doi: 10.1038/s41467-021-24836-9.
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.
自发性犬类癌症是有价值的，但相对研究较少且利用不足的模型。为了增强它们的使用，我们重新分析了已发表的 684 例>7 种常见肿瘤类型和>35 个品种的全外显子组和全基因组测序数据，进行了严格的质量控制和品种验证。我们的结果表明，犬类肿瘤的改变图谱是依赖于肿瘤类型的，但可能与品种无关。每种肿瘤类型都存在与人类肿瘤相对应的主要途径改变（例如，乳腺肿瘤中的 PI3K 和骨肉瘤中的 p53）。乳腺肿瘤和神经胶质瘤的肿瘤突变负担（TMB）较低（中位数<0.5 个突变/ Mb），而口腔黑色素瘤、骨肉瘤和血管肉瘤的 TMB 较高（中位数≥1 个突变/ Mb）。在肿瘤类型和品种中，TMB 与 TP53 的突变有关，但与突变频率最高的基因 PIK3CA 无关。金毛猎犬携带与 TMB 相关且富含骨肉瘤的突变特征。在这里，我们提供了一个主要肿瘤类型和品种的犬类突变的快照。
