Canine Somatic Mutations from Whole-Exome Sequencing of B-Cell Lymphomas in Six Canine Breeds—A Preliminary Study

SIMPLE SUMMARY: The aim of this study was to identify somatic mutations in dogs with B-cell lymphoma (BCL) using whole-exome sequencing (WES) and to investigate the impact of variants from lymph node (LN) aspirate samples compared with whole blood (WB) samples. This study analyzed DNA samples from eight dogs with BCL and conducted immunophenotyping using PCR for antigen receptor rearrangement (PARR). DNA was extracted and sequenced, and variant calling was performed. The analysis revealed highly common somatic variants, including a variant in the Golgi integral membrane protein 4 (GOLIM4) gene, which is associated with the endosome-to-Golgi protein trafficking pathway. Other notable variants were identified in genes such as desmocollin1 (DSC1), lipoxygenase homology domains 1 (LOXHD1), and glycoprotein VI platelet (GP6). The results suggest potential genetic markers and pathways involved in BCL in dogs. This study provides valuable insights into the genomic landscape of BCL in dogs, contributing to our understanding of the disease and potentially facilitating the development of targeted therapies in veterinary medicine. ABSTRACT: Canine lymphoma (CL) is one of the most common malignant tumors in dogs. The cause of CL remains unclear. Genetic mutations that have been suggested as possible causes of CL are not fully understood. Whole-exome sequencing (WES) is a time- and cost-effective method for detecting genetic variants targeting only the protein-coding regions (exons) that are part of the entire genome region. A total of eight patients with B-cell lymphomas were recruited, and WES analysis was performed on whole blood and lymph node aspirate samples from each patient. A total of 17 somatic variants (GOLIM4, ITM2B, STN1, UNC79, PLEKHG4, BRF1, ENSCAFG00845007156, SEMA6B, DSC1, TNFAIP1, MYLK3, WAPL, ADORA2B, LOXHD1, GP6, AZIN1, and NCSTN) with moderate to high impact were identified by WES analysis. Through a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of 17 genes with somatic mutations, a total of 16 pathways were identified. Overall, the somatic mutations identified in this study suggest novel candidate mutations for CL, and further studies are needed to confirm the role of these mutations.