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BIOMARKER:

B2M mutation

i
Other names: B2M, Beta-2-microglobulin
Entrez ID:
19d
Evolutionary selection identifies critical immune-relevant genes in lung cancer subtypes. (PubMed, Front Genet)
Negative selection differs between the two cohorts and is observed in endoplasmic reticulum aminopeptidase genes, ERAP1 and ERAP2 genes, and DNAM-1/TIGIT ligands. Targeting genes or molecular pathways under positive or negative evolutionary selection may permit new treatment options and increase the efficacy of current immunotherapy.
Journal • IO biomarker
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B2M (Beta-2-microglobulin) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2)
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B2M mutation
6ms
B2M and JAK1/2-mutated MSI-H Colorectal Carcinomas Can Benefit From Anti-PD-1 Therapy. (PubMed, J Immunother)
B2M and JAK1/2 loss-of-function mutations occur frequently in microsatellite instability-high CRC. Our study demonstrated that patients with CRC harboring B2M or JAK1/2 mutations should not be excluded from anti-PD-1 therapy.
Journal • Tumor Mutational Burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
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TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • JAK2 (Janus kinase 2) • B2M (Beta-2-microglobulin) • JAK1 (Janus Kinase 1)
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MSI-H/dMMR • TMB-L • B2M mutation
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MSK-IMPACT
7ms
Genomic correlates of response to immune checkpoint blockade in Epstein-Barr virus-associated pulmonary lymphoepithelioma-like carcinoma (AACR 2022)
Our study observed comprehensive CNVs in PLELC patients which is a unique molecular feature compared with other NSCLC subtypes and EBV-positive NPC. Higher TMB level and amplifications of B2M in PLELC patients may be used as potential biomarkers to indicate better treatment responses to ICIs.
Checkpoint inhibition • Tumor Mutational Burden • IO biomarker
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TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • B2M (Beta-2-microglobulin) • TNFAIP3 (TNF Alpha Induced Protein 3) • TGFB1 (Transforming Growth Factor Beta 1) • CDKN1B (Cyclin dependent kinase inhibitor 1B) • NFKBIA (NFKB Inhibitor Alpha 2)
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TMB-H • B2M mutation • TNFAIP3 mutation
12ms
Tracking the evolution of untreated high-intermediate/high-risk diffuse large B-cell lymphoma by circulating tumour DNA. (PubMed, Br J Haematol)
Analysis of dynamic blood samples confirmed the utility of ctDNA for the real-time assessment of treatment response and revealed that the increases in ctDNA levels and changes in KMT2D mutation status could be useful predictors of disease progression. Our present results suggest that ctDNA is a promising method for the detection of mutation spectrum and serves as a biomarker for disease monitoring and predicting clinical recurrence.
Journal • Circulating tumor DNA
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TP53 (Tumor protein P53) • KMT2D (Lysine Methyltransferase 2D) • B2M (Beta-2-microglobulin) • CREBBP (CREB binding protein) • CARD11 (Caspase Recruitment Domain Family Member 11) • TNFAIP3 (TNF Alpha Induced Protein 3)
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TP53 mutation • KMT2D mutation • B2M mutation
over1year
Beta-2-microglobulin Mutations Are Linked to a Distinct Metastatic Pattern and a Favorable Outcome in Microsatellite-Unstable Stage IV Gastrointestinal Cancers. (PubMed, Front Oncol)
Eighteen patients received ICB with pembrolizumab and one patient with nivolumab/ipilimumab. Among metastatic MSI GI cancers, B2M-mutant tumors represent a biologically distinct disease with distinct metastatic patterns. To assess ICB response in B2M-mutant MSI cancer patients, future studies need to account for the fact that baseline survival of patients with B2M-mutant MSI cancer may be longer than of patients with B2M-wild type MSI cancer.
Journal • PD(L)-1 Biomarker
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B2M (Beta-2-microglobulin)
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B2M mutation
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Keytruda (pembrolizumab) • Opdivo (nivolumab) • Yervoy (ipilimumab)
over1year
[VIRTUAL] Beta 2 microglobulin deficiency does not preclude response to combined CTLA-4 and PD1 blockade in mismatch repair deficient murine cancers (EACR 2021)
We highlight the role of tumor associated effector CD4+ T cells in pre-clinical models and patients with impaired APM. Overall, our findings highlight that the absence of B2M in MMRd cancers, does not prevent clinic response to immune checkpoint blockade.
Preclinical • Mismatch repair • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • MLH1 (MutL homolog 1) • B2M (Beta-2-microglobulin) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • CD4 (CD4 Molecule)
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MSI-H/dMMR • B2M mutation • MLH1 deletion
almost2years
Influence of oncogenic mutations and tumor microenvironment alterations on extranodal invasion in diffuse large B-cell lymphoma. (PubMed, Clin Transl Med)
Our findings thus contribute to an improved understanding of the biological behavior of multiple ENI and provide a clinical rationale for targeting ENI in DLBCL.
Journal
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ARID1A (AT-rich interaction domain 1A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • B2M (Beta-2-microglobulin) • CD79B (CD79b Molecule) • FOXO1 (Forkhead box O1) • PIM1 (Pim-1 Proto-Oncogene)
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ARID1A mutation • MYD88 mutation • CD79B mutation • B2M mutation • PIM1 mutation
almost2years
[VIRTUAL] Single-Cell Analysis of the Classical Hodgkin Lymphoma Immune Environment Reveals a Clonally-Expanded CD8+ T Cell Population with a Cytotoxic Phenotype (ASH 2020)
For the first time, our data have unveiled the nature of the T cell repertoire in cHL at single cell resolution. Our results reveal a recurrent pattern of clonal expansion within effector CD8+ cells, which may be the HRS antigen-specific T cells that mediate response to PD-1 blockade. This hypothesis requires confirmation through similar analyses of pre- and on-treatment biopsies of cHL patients receiving anti-PD-1 therapy.
Clinical • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CD19 (CD19 Molecule) • IFNG (Interferon, gamma) • B2M (Beta-2-microglobulin) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • GZMA (Granzyme A)
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PD-L1 overexpression • PD-L1 amplification • B2M mutation
almost2years
The shared frameshift mutation landscape of microsatellite-unstable cancers suggests immunoediting during tumor evolution. (PubMed, Nat Commun)
Importantly, certain outlier mutations are common in MSI cancers despite being related to frameshift peptides with functionally confirmed immunogenicity, suggesting a possible driver role during MSI tumor evolution. Neoantigens resulting from shared mutations represent promising vaccine candidates for prevention of MSI cancers.
Journal
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MSI (Microsatellite instability) • B2M (Beta-2-microglobulin)
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B2M mutation
2years
Genetic and epigenetic analysis of the beta-2-microglobulin gene in microsatellite instable colorectal cancer. (PubMed, Clin Exp Med)
Methylation of the promoter region of the B2M gene was observed in one patient with MSI-H colorectal cancer. Detection of genetic and epigenetic changes in B2M gene could be important in personalized therapy for CRC patients as these changes may be one of the mechanisms of secondary resistance of MSI positive tumors to immunotherapy.
Journal • MSi-H Biomarker
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BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • MSI (Microsatellite instability) • B2M (Beta-2-microglobulin)
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KRAS mutation • MSI-H/dMMR • BRAF mutation • B2M mutation • TILs
over2years
Implications of Hereditary Origin on the Immune Phenotype of Mismatch Repair-Deficient Cancers: Systematic Literature Review. (PubMed, J Clin Med)
The quantitative and qualitative differences clearly indicate a distinct biology of sporadic and hereditary MSI tumors. Clinically, these findings underline the need for differentiating sporadic and hereditary tumors in basic science studies and clinical trials, including trials evaluating immune checkpoint blockade therapy in MSI tumors.
Review • Journal
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MSI (Microsatellite instability) • B2M (Beta-2-microglobulin)
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MSI-H/dMMR • B2M mutation
over2years
Molecular profiling of Chinese R-CHOP treated DLBCL patients: identifying a high-risk subgroup. (PubMed, Int J Cancer)
Next, we investigated mutation landscape in patients with wild-type (WT) TP53 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior TTP than those with WT or non-265P (P = 0.046). This study reveals the mutation spectrum of treatment-naive Chinese DLBCL patients.It also confirms the clinical significance of TP53 mutations and indicates the prognostic value of MYD88 L265P in TP53 WT patients.
Clinical • Journal
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TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • KMT2D (Lysine Methyltransferase 2D) • B2M (Beta-2-microglobulin)
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TP53 mutation • B2M mutation
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Rituxan (rituximab)
over2years
[VIRTUAL] Neoantigen screening identifies EGFR L858R mutation immunogenicity in 1862 Chinese NSCLC patients. (ASCO 2020)
(1) Targeting EGFR L858R mutation in patients with HLA-A*33:03 allele appeared to be valuable for the neoantigen-based vaccine designed for Chinese NSCLC patients. (2) The specific immunogenicity of L858R seemed to be little influenced by B2M mutation and HLA-I LOH which were important factors for neoantigen presentation. (3) High pDC and low neutrophils infiltration might contribute to the inhibitive microenvironment associated with L858R mutation.
Clinical
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EGFR (Epidermal growth factor receptor) • B2M (Beta-2-microglobulin)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • B2M mutation • EGFR L858R + EGFR exon 19 deletion
over2years
Sequential treatment failures in response to BRAF/MEK and immune checkpoint inhibitors mediated by MAP2K2 and B2M mutations in melanoma. (PubMed, Exp Mol Pathol)
Here, we describe a patient with BRAF-V600E-positive metastatic melanoma who was sequentially treated with BRAF/MEK inhibitors (dabrafenib/trametinib) and checkpoint inhibitor immunotherapy (nivolumab, followed by pembrolizumab). After the emergence of resistance, whole exome sequencing was performed, implicating MAP2K2 and B2M mutations in loss of response to anti-BRAF/MEK and anti-PD1 therapies, respectively.
Journal • Checkpoint inhibition • PD(L)-1 Biomarker
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BRAF (B-raf proto-oncogene) • B2M (Beta-2-microglobulin)
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BRAF V600 • B2M mutation
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Keytruda (pembrolizumab) • Opdivo (nivolumab) • Mekinist (trametinib) • Tafinlar (dabrafenib)