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.

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% 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
	1-EE¹	high-confidence DLBCL gene²
	1-EE	high-confidence FL gene
	2	relevance in PMBL/cHL/GZL not firmly established³
	2	relevance in BL not firmly established⁴

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)
BL	Yes	No	0.000
DLBCL	Yes	Yes	2.645
FL	Yes	No	1.197

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

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

Bal E, Kumar R, Hadigol M, Holmes AB, Hilton LK, Loh JW, Dreval K, Wong JCH, Vlasevska S, Corinaldesi C, Soni RK, Basso K, Morin RD, Khiabanian H, Pasqualucci L, Dalla-Favera R. Super-enhancer hypermutation alters oncogene expression in B cell lymphoma. Nature. 2022 Jul;607(7920):808–815. PMCID: PMC9583699

Tanaka S, Louie DC, Kant JA, Reed JC. Frequent incidence of somatic mutations in translocated BCL2 oncogenes of non-Hodgkin’s lymphomas. Blood. 1992 Jan 1;79(1):229–237.

Sarkozy C, Hung SS, Chavez EA, Duns G, Takata K, Chong LC, Aoki T, Jiang A, Miyata-Takata T, Telenius A, Slack GW, Molina TJ, Ben-Neriah S, Farinha P, Dartigues P, Damotte D, Mottok A, Salles GA, Casasnovas RO, Savage KJ, Laurent C, Scott DW, Traverse-Glehen A, Steidl C. Mutational landscape of gray zone lymphoma. Blood. 2021 Apr 1;137(13):1765–1776.

Burkhardt B, Michgehl U, Rohde J, Erdmann T, Berning P, Reutter K, Rohde M, Borkhardt A, Burmeister T, Dave S, Tzankov A, Dugas M, Sandmann S, Fend F, Finger J, Mueller S, Gökbuget N, Haferlach T, Kern W, Hartmann W, Klapper W, Oschlies I, Richter J, Kontny U, Lutz M, Maecker-Kolhoff B, Ott G, Rosenwald A, Siebert R, von Stackelberg A, Strahm B, Woessmann W, Zimmermann M, Zapukhlyak M, Grau M, Lenz G. Clinical relevance of molecular characteristics in Burkitt lymphoma differs according to age. Nat Commun. 2022 Jul 6;13(1):3881. PMCID: PMC9259584