The K9 lymphoma assay allows a genetic subgrouping of canine lymphomas with improved risk classification

Abstract We developed a targeted next-generation sequencing approach designed for the genomic classification of canine lymphoma. Positioned within the evolving landscape of comparative and veterinary oncology, this study underscores the clinical significance of tailored genetic profiling for this tumor in dogs, marking a crucial step in diagnostic high-throughput genetic analysis. Leveraging a previous dataset, the “K9 lymphoma assay” demonstrated robust comparability and reproducibility in canine diffuse large B-cell lymphoma (DLBCL), when matched with previously tumors examined through whole-exome sequencing. Expanding our investigation to encompass several B- and T-cell lymphoma histotypes, we unveiled distinct mutational landscapes distinguishing nodal lymphomas derived from immature lymphocytes and nodal lymphomas originating from mature lymphocytes. TRAF3 was the most frequently altered gene in B-cell lymphomas, exhibiting unique mutational patterns. Key genetic events, such as TP53 and SETD2 mutations, clinically demonstrated universal implications across B-cell lymphomas, positioning them as potential prognostic and therapeutic indicators. These findings advocate for a tailored therapeutic approach directly impacting treatment decisions and outcomes in managing canine lymphomas. Our study provides the largest and most comprehensive genomic characterization of clinically staged canine lymphomas to date, and it provides pivotal insights for future research and therapeutic strategies in comparative oncology.