Structural variations of BCL2 specifically increase BCL2 expression in a subtype-dependent manner. (A) Box plot demonstrating the association of BCL2 gene expression with structural variations of BCL2 locus. Protein expression demonstrated with dot colors. Representative cases of the cytogenic alterations (FISH) are shown below the plot. (A-D) Break-apart positive cases by FISH with concurrent copy number alterations regraded BCL2^TL. (B) Association of BCL2 immunoreactivity with underlying structural variations. (C) Oncoprints of BCL2 alterations demonstrating mutually exclusive nature of BCL2^TL and BCL2^GA. Coding single-nucleotide variations (SNVs) of BCL2 were cooccurring with BCL2^TL (Fisher’s exact, P = 8.5E-5). Interestingly, patients with cooccurring BCL2^GA and BCL2 SNVs represented GCB subtype. (D-E) Volcano plots demonstrating the differentially expressed genes between BCL2 altered and other tumors within the RNA sequencing-based molecular subtypes. BCL2 alteration associated genes shown with a positive fold change. (D) BCL2^TL within GCB DLBCLs. (E) BCL2^GA within ABC DLBCLs. Most of the BCL2^GA-associated upregulated genes resided in the vicinity of BCL2 in 18q locus (black dots). ****P < .0001. ns, not significant.