Identification of somatic mutations in lymphomas of Bernese Mountain dogs

Canine lymphoma closely resembles the human counterpart and therefore serves as a translational animal model for comparative and translational research. Bernese Mountain dogs (BMDs) are historically predisposed to developing lymphoma, however the somatic mutational profile in this breed has not yet been defined. We analysed 27 BMD lymphoma samples from the Michigan State University Bernese Mountain Dog DNA and Tissue Repository, investigating mutations in 499 cancer-related genes, using a targeted gene panel. Somatic mutations were detected in 96.3% of cases, most frequently affecting TRAF3 (25.9%), TP53 , EP300 , and MYC (22% each), and MAP3K14 (19%). Copy number variations were identified in 66% of samples, with recurrent alterations in KMT2C, PIK3R1, TP53, MTAP, PTEN, MET, NRG1, PTPN11, SCRN1 , and SETD2 . We report a genetic profile in BMD lymphoma that is shared with other breeds, as well as breed-specific alterations, like in the EP300 gene. These findings may aid in future treatment approaches, and novel prognostic biomarkers for the breed with potential implications for comparative oncology and translational research.