Abstract: Hepatocellular carcinoma (HCC) is the most prevalent primary liver tumor in dogs, with no effective treatment for non-resectable disease. To pave the way for the development of targeted therapeutics and to assess the translational value of the disease, it is imperative to study the genomic makeup of canine HCC. We aim to describe mutations in canine HCC, and draw comparisons with commonly affected genes and pathways in human HCC. Tumor tissues from 40 dogs diagnosed with HCC were collected via retrospective study of biobanked material, and through clinical cases submitted to Vidium. Forty HCC tumor samples were analyzed by SearchLight DNATM, a 120-gene sequencing panel validated to detect common cancer mutations. Mutations were annotated by Vidium InsightTM, a comprehensive canine precision oncology knowledgebase, for the prediction of their roles in HCC pathogenicity and clinical relevance for diagnosis, prognosis and treatment. We identified 445 (155 unique) mutations in 67 genes. The mean and median mutation burden per case were 11 and 9, respectively (range: 1-35). TP53, CDKN2B, CTNNB1, APC and ATM were the most commonly mutated genes. Equivalent mutations in over 20 genes are known to be pathogenic in human HCC, and these genes are enriched in WNT/β-catenin, cell cycle, and chromatin remodeling pathways.Our data revealed several molecular subtypes exhibiting unique mutation profiles in canine HCC. Prevalent mutations in the WNT/β-catenin signaling resemble those found in human disease, highlighting the translational value of the canine disease as a model for human HCC.
