BCL2

Overview

BCL2 encodes an anti-apoptotic protein canonically deregulated in B-cell lymphomas via Ig-locus translocations and targeted by venetoclax in CLL.

Alterations observed in the corpus

  • Recurrent immunoglobulin-locus translocation partner predominantly in IGHV-mutated CLL (5/88 WGS cases, 5.7%), arising via aberrant V(D)J recombination; additional cases identified by WES PMID:35927489.
  • BCL2 translocation enriched in EZB DLBCL subtype (81% of EZB cases) in a real-world LymphGen classification validation study using MSK-IMPACT Heme (400-gene panel, 241 DLBCL patients); BCL2 translocation is a robust single-gene classifier for the EZB molecular subtype PMID:38497151.
  • Identified as recurrently mutated in DLBCL and FL by whole-genome/exome sequencing of non-Hodgkin lymphomas PMID:21796119
  • Identified as a recurrently mutated gene in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing of 55 tumors PMID:22343534
  • Recurrent translocation involving BCL2 detected by low-pass WGS in 5/106 endometrial carcinoma tumors (ucec_tcga_pub); predicted in-frame fusions with increased BCL-family expression PMID:23636398
  • Cited as a DLBCL driver gene in the context of somatic-hypermutation discussion in multiple myeloma (MM); BCL2 invoked by analogy alongside MYD88 and CARD11 as DLBCL drivers that appear as rare mutations in MM patients lacking the 11 canonical MM driver mutations PMID:24434212
  • Focal amplification (GISTIC peak) in thymic tumors with correlated increased mRNA expression by RNA-seq PMID:24974848
  • Highest median protein expression in Triple-WT melanoma subtype by RPPA; rationale for BH3 mimetics in Triple-WT PMID:26091043
  • Identified as a putative MYB transcriptional target gene in adenoid cystic carcinoma (ACC); MYB binding genome-wide (13,278 high-confidence peaks) drives a transcriptional program that includes BCL2 as one of its targets PMID:26829750
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Cancer types (linked)

  • CLL — BCL2 translocations are an M-CLL-biased structural variant class in the integrated CLL map PMID:35927489.
  • DLBCLNOS — BCL2 translocation defines EZB subtype (81% prevalence); detectable with 400-gene clinical NGS panel PMID:38497151.

Co-occurrence and mutual exclusivity

  • BCL2 translocations co-segregate with the M-CLL molecular subtype rather than with U-CLL PMID:35927489.

Therapeutic relevance

  • BCL2 is the molecular target of venetoclax, one of the contemporary CLL therapies cited as shifting the prognostic landscape of TP53-mutated disease in the era of ibrutinib/venetoclax PMID:35927489.

Open questions

  • Whether BCL2-translocated M-CLL has distinct venetoclax response kinetics is not resolved in the corpus PMID:35927489.

Sources

This page was processed by crosslinker on 2026-05-09. - PMID:21796119

This page was processed by crosslinker on 2026-05-09. - PMID:22343534

This page was processed by crosslinker on 2026-05-09. - PMID:23636398

This page was processed by crosslinker on 2026-05-09. - PMID:24434212

This page was processed by crosslinker on 2026-05-09. - PMID:24974848

This page was processed by wiki-cli on 2026-05-11. - PMID:26091043

This page was processed by wiki-cli on 2026-05-14. - PMID:26829750

This page was processed by wiki-cli on 2026-05-14. - PMID:28985567

This page was processed by wiki-cli on 2026-05-15.