BCL2 - morinlab/LLMPP GitHub Wiki

bibliography: 'morinlab.bib' csl: 'NLM.csl' link-citations: true

BCL2

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. Although missense 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.

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timeline
    title Publication timing
      1992-01-01 : Tanaka : DLBCL
      2011-07-27 : Morin : FL
      2021-04-01 : Sarkozy : PMBL
      2022-07-06 : Burkhardt : BL

Relevance tier by entity

Entity Tier Description
DLBCL 1-EE[@balSuperenhancerHypermutationAlters2022] high-confidence DLBCL gene [@tanakaFrequentIncidenceSomatic1992]
FL 1-EE high-confidence FL gene
PMBL 2 relevance in PMBL/cHL/GZL not firmly established[@sarkozyMutationalLandscapeGray2021a]
BL 2 relevance in BL not firmly established[@burkhardtClinicalRelevanceMolecular2022b] 
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Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity source frequency (%)
BL GAMBL genomes+capture 0.46
BL Thomas cohort 0.00
BL Panea cohort 1.00
DLBCL GAMBL genomes 23.71
DLBCL Schmitz cohort 10.60
DLBCL Reddy cohort 12.90
DLBCL Chapuy cohort 15.80
FL GAMBL genomes 50.35

Mutation pattern and selective pressure estimates

Entity aSHM Significant selection dN/dS (missense) dN/dS (nonsense)
BL Yes No 0.000 0
DLBCL Yes Yes 2.645 0
FL Yes No 1.197 0

aSHM regions

chr_name hg19_start hg19_end region regulatory_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

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

BCL2 Expression

References

  1. Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, L