BCL2 aSHM is an accurate proxy for BCL2-Rs. (A) Summary of sequencing types across lymphoma entities. (B) Percentage of rearrangements identified by BA-FISH that were identified in sequencing data. (C-E) Architecture of BCL2-Rs in FL (C), DLBCL (D), and HGBCL-DH-BCL2 (E). In each plot, the outermost ring gives the chromosome ideogram, followed by a genomic coordinate scale, a gene coordinate track, and a rainfall plot of intermutation distance with points colored according to whether the mutation overlaps the canonical AID WRCY motif (red) or not (black). Mutations are only shown in regions covered by the targeted capture panel and include tumors without rearrangements. Innermost lines show the linkages between BCL2 and the most common rearrangement partners. (F) BCL2 expression by RNAseq stratified by BCL2-R status. FDR-corrected Wilcoxon tests were used to compare the expression of each group with DLBCLs without BCL2-R. ∗∗P < .01; ∗∗∗∗P < .0001. (G) Mutation count at the BCL2 TSS stratified by lymphoma entity and BCL2 FISH status. The x-axis indicates the presence of a rearrangement determined by sequencing. The horizontal black line indicates the optimal cutoff of 3.5 mutations for predicting the presence of a BCL2-R. The total number and percentage of tumors with mutations over the cutoff are indicated above each group. (H-I) Receiver operating characteristic (ROC) curves giving sensitivity and specificity of BCL2 mutation counts at the TSS (H) or within exon 1 (I) to predict BCL2 rearrangement status. The red point is labeled with the Youden optimal cutoff (sensitivity and specificity). AUC, area under the curve; FDR, false detection rate; ND, not done; NEG, negative; POS, positive; TSS, transcription start site.