Recurrent focal deletions of the TRAF3 locus in hDLBCL. (A) A panel of 148 diagnostic hDLBCL tumors were analyzed for copy number alterations using genotyping arrays (Materials and methods). Loss of TRAF3 was detected in 13 cases with the smallest deletion encompassing a region ∼600 kb in length and showing a minimal common region comprising RCOR1, TRAF3, AMN, and CDC42BPB. This region was deemed significant by the GISTIC algorithm (residual Q-value: 0.00053462). Although COO subgroup information was not available for all patients, TRAF3 deletions were detected in a total of 6 ABC cases and 2 GCB cases. (B) The deletion was verified using FISH and probes specific to TRAF3 (red) and IGH probes acting as a control (green). In the tumor sample tested, loss of TRAF3, as indicated by a single red signal, was observed in 83% of cells. Loss of only a single copy of IGH, resulting in a single green signal, was also observed in the malignant cells. (C) Using RNA-seq data from 91 of the samples with such data available, we compared the expression level of TRAF3 in cases with loss of the locus relative to undeleted cases. Using this approach, TRAF3 mRNA was significantly less abundant among deleted cases and also significantly reduced relative to benign tissues (flow-sorted centroblast samples).