B2M

Overview

The B2M (β2-microglobulin) gene plays a crucial role in the function of the major histocompatibility complex (MHC) class I molecules, which are essential for immune system recognition of infected or malignant cells. B2M mutations in B-cell lymphomas, particularly in DLBCL and PMBCL, lead to reduced MHC class I expression, enabling tumor cells to evade immune detection and destruction by cytotoxic T cells. ## History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2011-07-27 : Morin : FL 2015-02-12 : Reichel : PMBL 2020-07-30 : Pararajalingam : MCL

Relevance tier by entity

Entity	Tier	Description
	1	high-confidence PMBL/cHL/GZL gene
	1	high-confidence DLBCL gene
	1	high-confidence FL gene
	2	relevance in MCL not firmly established

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
BL	GAMBL genomes+capture	2.31
BL	Thomas cohort	2.50
BL	Panea cohort	3.00
DLBCL	GAMBL genomes	15.11
DLBCL	Schmitz cohort	15.53
DLBCL	Reddy cohort	12.11
DLBCL	Chapuy cohort	11.97
FL	GAMBL genomes	8.55
MCL	GAMBL genomes	1.42

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	No	No	9.379	56.571
DLBCL	No	Yes	60.843	340.788
FL	No	Yes	54.190	326.834

## B2M Hotspots

Chromosome	Coordinate (hg19)	ref>alt	HGVSp
chr15	45003745	A>G	M1?
chr15	45003745	A>T	M1?
chr15	45003745	AGATGTCT>-	NA
chr15	45003746	T>A	M1?
chr15	45003746	T>C	M1?
chr15	45003746	T>G	M1?
chr15	45003747	G>A	M1?
chr15	45003747	G>C	M1?
chr15	45003758	T>A	V5E
chr15	45003761	C>A	A6D
chr15	45003764	T>C	L7S
chr15	45003764	T>G	L7*
chr15	45003766	G>C	A8P
chr15	45003767	C>A	A8D
chr15	45003770	T>A	V9E
chr15	45003770	T>G	V9G
chr15	45003779	T>A	L12Q
chr15	45003779	T>C	L12P
chr15	45003779	T>G	L12R
chr15	45003781	C>T	L13F
chr15	45003782	T>C	L13P

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

B2M 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, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJM, Connors JM, Hirst M, Gascoyne RD, Marra MA. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011 Jul 27;476(7360):298–303. PMCID: PMC3210554
Reichel J, Chadburn A, Rubinstein PG, Giulino-Roth L, Tam W, Liu Y, Gaiolla R, Eng K, Brody J, Inghirami G, Carlo-Stella C, Santoro A, Rahal D, Totonchy J, Elemento O, Cesarman E, Roshal M. Flow sorting and exome sequencing reveal the oncogenome of primary Hodgkin and Reed-Sternberg cells. Blood. 2015 Feb 12;125(7):1061–1072. PMID: 25488972
Pararajalingam P, Coyle KM, Arthur SE, Thomas N, Alcaide M, Meissner B, Boyle M, Qureshi Q, Grande BM, Rushton C, Slack GW, Mungall AJ, Tam CS, Agarwal R, Dawson SJ, Lenz G, Balasubramanian S, Gascoyne RD, Steidl C, Connors J, Villa D, Audas TE, Marra MA, Johnson NA, Scott DW, Morin RD. Coding and noncoding drivers of mantle cell lymphoma identified through exome and genome sequencing. Blood. 2020 Jul 30;136(5):572–584. PMCID: PMC7440974