BCL2 - morinlab/LLMPP GitHub Wiki
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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](https://github.com/morinlab/LLMPP/wiki/images/icons/DLBCL_tier1.png) |
1-EE[@balSuperenhancerHypermutationAlters2022] |
high-confidence DLBCL gene [@tanakaFrequentIncidenceSomatic1992] |
![FL](https://github.com/morinlab/LLMPP/wiki/images/icons/FL_tier1.png) |
1-EE |
high-confidence FL gene |
![PMBL](https://github.com/morinlab/LLMPP/wiki/images/icons/PMBL_tier2.png) |
2 |
relevance in PMBL/cHL/GZL not firmly established[@sarkozyMutationalLandscapeGray2021a] |
![BL](https://github.com/morinlab/LLMPP/wiki/images/icons/BL_tier2.png) |
2 |
relevance in BL not firmly established[@burkhardtClinicalRelevanceMolecular2022b] |
|
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
![](https://github.com/morinlab/LLMPP/wiki/images/proteinpaint/BCL2_NM_000633.svg)
View all variants in GenomePaint hg19 or hg38
![](https://github.com/morinlab/LLMPP/wiki/images/proteinpaint/BCL2.svg)
BCL2 Expression
![](https://github.com/morinlab/LLMPP/wiki/images/gene_expression/BCL2_by_pathology.svg)
References
- 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