Characterization of the genetic landscape of feline oral squamous cell carcinoma

Over 94 million domestic cats are susceptible to cancers and other common and rare diseases. While cancer treatment in cats increasingly mirrors that available in humans, treatment failures are more frequent. There are no FDA or USDA approved cancer drugs for cats and a paucity of cancer treatments beyond surgery, radiotherapy, and cytotoxic chemotherapy indicate an urgent need to define the molecular properties of aggressive feline cancers including common cancers such as soft tissue sarcoma, mammary carcinoma, lymphoma, and feline oral squamous cell carcinoma. Whole exome sequencing (WES) is a proven strategy to study these disease-causing variants in humans and other organisms. To examine the effectiveness of WES in the study of feline cancer and Mendelian diseases, whole exome sequencing was conducted on 41 cats with known and unknown genetic diseases and traits, of which ten cats had matching whole genome sequence (WGS) data available, used to validate WES performance. Within the 41 cats, we identified 31 previously known causal variants and discovered new gene candidate variants, including novel missense variance for polycystic kidney disease and atrichia in the Peterbald cat. The WES data was sufficient to identify novel gene candidate alleles for diseases and traits in a feline model. Feline oral squamous cell carcinoma (FOSCC) is a cancer of the squamous cell lining in the oral cavity and represents up to 80 percent of all oral cancers in cats, with a low one-year survival rate of