Targeted sequencing of cBCLs identifies frequent mutations that affect MYC stability. (A) Frequently mutated genes identified in cBCL. Mutations observed across 86 canine BCL samples in 9 genes. After removing suspected germline variants,¹²  cBCLs had between 0 and 9 mutations (mean, 2.02) in genes of interest. Mutation frequencies of POT1 (15%), TP53 (14%), and SETD2 (13%) are similar to those reported in previous studies.^15,16 MAP3K14 mutations occur in 14% of cases; however, its frequency in other studies has not been reported.¹⁵  (B) Spatial distribution of mutations observed in MYC, compared with human DLBCL. The odds ratio corresponding to the proportion of MYC hotspot mutations in cBCL vs hDLBCL is 30.79 (95% confidence interval [CI], 6.73-202.3; P = 1.21 × 10⁻⁷). (C) The MYC phosphodegron sequence is highly conserved in vertebrates and the most common site of MYC mutations in cBCL (12 of 15 mutations). (D) MYC and FBXW7 mutations do not co-occur in cBCL. (E) Spatial distribution of mutations observed in FBXW7, as compared with human DLBCL. The hotspot (present in both human and canine BCL) occurs in a WD40 repeat, which forms one of the blades of the β-propellor and affects a residue forming part of the substrate recognition domain.