Bailey A. Francis, Latasha Ludwig, Chang He, Melanie Dobromylskyj, Christof Bertram, Heike Aupperle‐Lellbach, Hannah Wong, Aiden Foster, Mark J Arends, Alejandro Suárez-Bonnet, Simon L. Priestnall, Laetitia Tatiersky, Fernanda Castillo-Alcala, Angie Rupp, Arlene Khachadoorian, Eda Parlak, Marine Inglebert, Shevaniee Umamaheswaran, Saamin Cheema, Martin Del Castillo Velasco-Herrera, Kim Wong, Ian Vermes, Jamie Billington, Sven Rottenberg, Geoffrey A. Wood, David J. Adams, Louise van der Weyden
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. TP53 was the most frequently mutated gene, and the most recurrent copy number alterations were loss of PTEN or FAS or gain of MYC . 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.