Table of Contents

Overview

BCL2 mutations are frequently found in DLBCL, particularly in the germinal center B-cell (GCB) subtype, and are often located in the flexible loop domain and outside the BCL2-homology domains. These mutations are caused by the somatic hypermutation process. The presence of these mutations are strongly correlated with the presence of a translocation between BCL2 and one of the immunoglobulin loci. Selective pressure analysis did not identify this gene as significantly enriched for either missense or truncating mutations, indicating that many of these mutations may represent passengers. Although mutations may not be under positive selective pressure in the context of lymphomagenesis, some of these mutations may interfere with the function of BCL2 antagonists.

Relevance tier by entity

Entity Tier Description
BL 2 Role of BCL2 mutations in BL requires confirmation
DLBCL 1 High-confidence DLBCL gene
FL 1 High-confidence FL gene
PMBL 2 Role of BCL2 mutations in PMBL requires confirmation

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 174 0.1598 [0.138,0.1815]
DLBCL GAMBL with Reddy 2,088 303 0.1451 [0.13,0.1602]
DLBCL BC 231 50 0.2165 [0.1633,0.2696]
DLBCL Dana-Farber 303 53 0.1749 [0.1321,0.2177]
DLBCL NCI 470 50 0.1064 [0.0785,0.1343]
DLBCL Reddy 999 129 0.1291 [0.1083,0.1499]
DLBCL DLBCL_ICGC 85 21 0.2471 [0.1554,0.3387]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 281 0.4377 [0.3993,0.4761]
FL GAMBL with Crouch 1,189 542 0.4558 [0.4275,0.4842]
FL BC 379 184 0.4855 [0.4352,0.5358]
FL Kalmbach 164 62 0.3780 [0.3038,0.4523]
FL Crouch 547 261 0.4771 [0.4353,0.519]
FL FL_ICGC 99 35 0.3535 [0.2594,0.4477]

BL

pathology Collection N mutated Incidence CI
BL GAMBL without Panea 309 1 0.0024 [0,0.0079]
BL GAMBL without ICGC/Zhou 320 2 0.0055 [0,0.0136]
BL GAMBL with Panea 410 2 0.0030 [0,0.0082]
BL BLGSP 219 1 0.0046 [0,0.0135]
BL Zhou/ICGC 90 0 0.0011 [0,0.008]
BL Panea 101 1 0.0099 [0,0.0292]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 1.4784 0 1
FL 1.1511 0 0
DLBCL 0.3993 0 0

aSHM regions

Chromosome hg19_start hg19_end Region Comment
chr18 60796984 60814103 intron strong_enhancer
chr18 60982728 60988342 TSS active_promoter

BCL2 Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr18 60985854 T>C M16V
chr18 60985854 T>A M16L
chr18 60985853 A>T M16K
chr18 60985852 C>T M16I
chr18 60985849 C>G K17N
chr18 60985842 G>A H20Y
chr18 60985840 A>C H20Q
chr18 60985838 T>G Y21S
chr18 60985835 T>C K22R
chr18 60985834 CT>TC K22R

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Expression

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References

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Citing

If you use the information or data from this site, please cite

Krysta Coyle, Kostiantyn Dreval, Daniel Hodson and Ryan D. Morin. Audit of B-cell cancer genes. Blood Adv (2025) 9 (8): 2019–2031.

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