Identification of novel genetic mutations for the treatment prognostication of canine lymphoma.

Canine lymphoma, a phenotypically and genetically heterogeneous disease, represents a significant proportion of canine cancers. We present a large-scale study of 238 dogs with lymphoma to better understand the genetic landscape of canine lymphoma, as well as the relationship to clinical outcomes. Using a targeted next-generation sequencing panel comprising 308 genes, we screened somatic and germline mutations in matched tumor and normal samples. Our findings revealed key associations between genetic alterations and lymphoma subtypes, with certain somatic variants linked to significant differences in response to common chemotherapy regimens. Recurrent mutations in genes such as KMT2C, KMT2D, NOTCH2, TRAF3, CCND1, ARID1A, CREBBP, and TP53 were observed, with TRAF3 mutations standing out for their significant association with prolonged progression-free survival and overall survival in B-cell lymphomas. In contrast, mutations in PIK3CD and CREBBP were associated with inferior outcomes in T-cell lymphomas, highlighting the immunophenotype-specific impact of genetic alterations on treatment responses. These findings support the integration of comprehensive genomic profiling in planning treatment strategies and optimizing clinical outcomes in canine lymphomas.