Table of Contents

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
BL 2 Role of B2M mutations in BL requires confirmation
DLBCL 1 High-confidence DLBCL gene
FL 1 High-confidence FL gene
MCL 2 Role of B2M mutations in MCL requires confirmation
PMBL 1 High-confidence PMBL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 156 0.1433 [0.1224,0.1641]
DLBCL GAMBL with Reddy 2,088 277 0.1327 [0.1181,0.1472]
DLBCL BC 231 29 0.1255 [0.0828,0.1683]
DLBCL Dana-Farber 303 38 0.1254 [0.0881,0.1627]
DLBCL NCI 470 73 0.1553 [0.1226,0.1881]
DLBCL Reddy 999 121 0.1211 [0.1009,0.1414]
DLBCL DLBCL_ICGC 85 16 0.1882 [0.1051,0.2713]

FL

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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

1.
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
2.
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
3.
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
4.
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.

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