The oncogenome of the domestic cat

Cancer is a common cause of morbidity and mortality in domestic cats. Because the mutational landscape of domestic cat tumors remains uncharacterized, we performed targeted sequencing of 493 feline tumor-normal tissue pairs from 13 tumor types, focusing on the feline orthologs of ~1000 human cancer genes. <i>TP53</i> was the most frequently mutated gene, and the most recurrent copy number alterations were loss of <i>PTEN</i> or <i>FAS</i> or gain of <i>MYC</i>. By identifying 31 driver genes, mutational signatures, viral sequences, and tumor-predisposing germline variants, our study provides insight into the domestic cat oncogenome. We demonstrate key similarities with the human oncogenome, confirming the cat as a valuable model for comparative studies, and identify potentially actionable mutations, aligning with a "One Medicine" approach.