Distribution of mutations in the Bcl-2 protein. (A) Schematic diagram of the BCL2 gene. Exons 1, 2, and 3 are color-coded in green, gray, and red, respectively. (B-D) Linear diagram of Bcl-2 protein showing Bcl-2 homology domains and distribution of amino acid alterations in (B) FL discovery (n = 38), (C) FL validation (n = 128), and (D) DLBCL (n = 39) cohorts. Color-coded symbols depict distinct types of alterations, with purple for synonymous, white for nonsynonymous with no charge introduction, red for nonsynonymous with introduction of a negative charge, and blue for nonsynonymous with introduction of a positive charge. (E) Overall BCL2 coding mutation frequency normalized for an interval of 10 amino acids in FL and DLBCL cohorts. (F) Two different projections of Bcl-2 are presented showing coding somatic mutations (red spheres) in the 2 FL cohorts mapped together onto the Bcl-2 3D structure (PDB 2O21). BH, Bcl-2 homology domain; FLD, flexible loop domain; TM, transmembrane domain.