Abstract
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.
Highlights
Spontaneous canine cancers are valuable but relatively understudied and underutilized models
Golden Retrievers are predisposed to the development of osteosarcoma, lymphoma and hemangiosarcoma; do the mutation landscape and tumor mutational burden (TMB) of Golden Retriever differ among these cancer types? Golden Retriever, Greyhound, and Rottweiler dogs are all predisposed to osteosarcoma; do the mutation landscape and TMB of osteosarcoma differ among these breeds? Addressing these questions will significantly enhance the usage of >300 pure breeds of the dog in cancer research
Our study consists of matched tumor and normal samples of 684 cases, which represent over 7 common canine tumor types and over 35 popular breeds, with published whole-exome sequencing (WES)[11,12,13,14,15,16,17,18,19] (654 cases) and/ or whole-genome sequencing (WGS) data[13,17,20] (86 cases)
Summary
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. Does canine tumor mutational burden (TMB) vary significantly among cancer types, as it does in human cancers5,6?. Golden Retrievers are predisposed to the development of osteosarcoma, lymphoma and hemangiosarcoma; do the mutation landscape and TMB of Golden Retriever differ among these cancer types? Across tumor types and breeds, TMB, defined as the number of somatic base substitutions and small indels per Mb callable coding sequence (CDS), is associated with mutation of TP53 but not PIK3CA, the two most mutated genes. Our study provides a snapshot of mutations across major tumor types and breeds in pet dogs
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