The prevalence and characterisation of TRAF3 and POT1 mutations in canine B-cell lymphoma

The genetic and mutational basis of canine lymphoma remains poorly understood. Several genes, including TRAF3 and POT1, are mutated in canine B-cell lymphoma (cBCL), and are likely involved in the pathogenesis of this disease. The purpose of this study was to assess the prevalence of TRAF3 and POT1 mutations in a cohort of dogs with cBCL, compared to dogs with non-cBCL diseases (including four dogs with T-cell lymphoma [cTCL]). Forty-nine dogs were included (n = 24 cBCL; n = 25 non-cBCL). Eleven dogs had matched non-tumour DNA assessed to determine if mutations were germline or somatic. All dogs had TRAF3 and POT1 assessed by Sanger sequencing. The prevalence of deleterious TRAF3 and POT1 mutations in cBCL was 36% and 17%, respectively. A deleterious TRAF3 mutation was suspected to be germline in 1/5 cases with matched non-tumour DNA available for comparison. Deleterious mutations were not found in specimens from the non-cBCL group. Several synonymous variants were identified in both genes in cBCL and non-cBCL samples, which likely represent polymorphisms. These results indicate TRAF3 and POT1 mutations are common in cBCL. Deleterious TRAF3 and POT1 mutations were only identified in dogs with cBCL, and not in dogs with non-cBCL diseases, suggesting they are important in the pathogenesis of cBCL. Future studies to investigate the prognostic and therapeutic implications of these mutations are required