B2M

Table of Contents

Overview
Experimental Evidence
Relevance tier by entity
Mutation incidence in large patient cohorts (GAMBL reanalysis)
Mutation pattern and selective pressure estimates
B2M Hotspots
Expression
References

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.

Experimental Evidence

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. This is often accompanied by mutations in the β2-Microglobulin gene, which further aids in immune evasion.¹

Relevance tier by entity

Entity	Tier	Description
	1	high-confidence PMBL/cHL/GZL gene²
	1	high-confidence DLBCL gene³
	1	high-confidence FL gene³
	2	relevance in MCL not firmly established⁴

Mutation incidence in large patient cohorts (GAMBL reanalysis)

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Mutation pattern and selective pressure estimates

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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

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Expression

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References

Challa-Malladi M, Lieu YK, Califano O, Holmes AB, Bhagat G, Murty VV, Dominguez-Sola D, Pasqualucci L, Dalla-Favera R. Combined genetic inactivation of Β2-Microglobulin and CD58 reveals frequent escape from immune recognition in diffuse large B cell lymphoma. Cancer Cell. 2011 Dec 13;20(6):728–740. PMCID: PMC3660995

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.

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

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