B2M

Overview

B2M encodes beta-2-microglobulin, an essential component of MHC class I; loss-of-function mutations drive immune escape in multiple lymphomas.

Alterations observed in the corpus

  • Mutated in ~32–33% of classic Hodgkin lymphoma cases in the combined 61-patient WGS+WES cohort, making it one of the most common cHL drivers PMID:36723991.
  • Evolutionary timing analysis placed B2M driver mutations before large chromosomal gains and whole-genome duplication, establishing them as early events in cHL pathogenesis PMID:36723991.
  • B2M mutated in 6% of dMMR/MSI-H gynecologic cancers treated with nivolumab (n=35); no enrichment of antigen-presenting machinery alterations in non-responders to PD-1 blockade PMID:38653864.
  • Focal deletions in 3 breast cancer metastasis tumors from 3 individuals; methylation rare (1 tumor) PMID:36585450
  • MHC class I component highly expressed in HGSOC Cancer.cell.3 cluster; subject to LOH-mediated loss as immune escape mechanism PMID:36517593
  • Identified as recurrently mutated in DLBCL and FL by whole-genome/exome sequencing of non-Hodgkin lymphomas PMID:21796119
  • Identified as a recurrently mutated gene in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing of 55 tumors PMID:22343534
  • Inactivating frameshift p.L13fs*10 found in one MCL case with concurrent 15q12–q21.1 deletion encompassing the locus; not observed in 97 additional patients including 3 with similar 15q monoallelic deletions PMID:24145436
  • MHC class I alteration enriched in the MSI subtype of gastric adenocarcinoma; B2M and HLA-B mutations consistent with antigen-presentation escape in microsatellite-unstable tumours PMID:25079317
  • Implicated in HLA-A/B antigen presentation pathway alterations in HNSCC; altered in 7% of HPV(-) and 11% of HPV(+) tumors (279-tumor TCGA HNSCC cohort) PMID:25631445
  • Homozygous deletion in individual PCNSL cases; contributes to immune-evasion through MHC-I loss in primary central nervous system lymphoma PMID:25991819
  • Component of MHC class I antigen-processing machinery; enriched for somatic mutations in TIL-rich colorectal carcinoma, consistent with immune-escape selection (Figure 6C, Table S10) PMID:27149842
  • Focally deleted in both lung ADC and SqCC; enriched for loss-of-function mutations (p < 0.01), Pan-Lung FDR q = 0.006; implicated in MHC-I antigen-presentation loss PMID:27158780
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  • A validation-cohort non-clinical-benefit (NCB) patient with PBRM1 LOF had a co-occurring B2M alteration, hypothesized to explain non-response to anti-PD-(L)1 therapy in ccRCC PMID:29301960.
  • Truncating B2M mutations were rare in a 240-patient NSCLC ICI cohort; one patient with biallelic deleterious B2M (S40* + Q28L) and confirmed loss of B2M IHC nonetheless had a PR ongoing at 8.9 months with TMB of 48 SNVs/Mb PMID:29337640.

Cancer types (linked)

  • Classic Hodgkin lymphoma — B2M is a top-tier HRS-cell driver and an immune-escape mechanism PMID:36723991.

Co-occurrence and mutual exclusivity

  • Co-occurs with the other early cHL drivers BCL7A, GNA13, and PTPN1 in the temporal window preceding large chromosomal gains PMID:36723991.

Therapeutic relevance

  • No direct therapy is evaluated, but B2M loss suggests MHC-class-I-dependent immunotherapy resistance in cHL PMID:36723991.

Open questions

  • How early B2M-mutant HRS clones interact with AID-driven mutagenesis and later WGD events remains to be mechanistically clarified PMID:36723991.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:36585450

This page was processed by crosslinker on 2026-05-14. - PMID:36517593

This page was processed by crosslinker on 2026-05-14. - PMID:21796119

This page was processed by crosslinker on 2026-05-14. - PMID:22343534

This page was processed by crosslinker on 2026-05-14. - PMID:24145436

This page was processed by crosslinker on 2026-05-14. - PMID:25079317

This page was processed by crosslinker on 2026-05-14. - PMID:25631445

This page was processed by crosslinker on 2026-05-14. - PMID:25991819

This page was processed by crosslinker on 2026-05-14. - PMID:27149842

This page was processed by entity-page-writer on 2026-05-15. - PMID:27158780

This page was processed by entity-page-writer on 2026-05-15. - PMID:29033130

This page was processed by wiki-cli on 2026-05-15. - PMID:29122777

This page was processed by wiki-cli on 2026-05-15. - PMID:29301960

This page was processed by wiki-cli on 2026-05-15. - PMID:29337640

This page was processed by wiki-cli on 2026-05-15.