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BIOMARKER:

B2M mutation

i
Other names: B2M, Beta-2-microglobulin
Entrez ID:
4ms
Antitumor Immune Responses in B2M-Deficient Cancers. (PubMed, Cancer Immunol Res)
We conclude that in the absence of B2M, activation of CD4+ T cells and NK cells can mediate responses to murine models of PD-1 blockade therapy. Additionally, in human melanoma the intratumoral presence of activated NK cells upon partial B2M loss likely selects against tumor escape through low surface MHC class I expression.
Journal • PD(L)-1 Biomarker • IO biomarker
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B2M (Beta-2-microglobulin) • CD4 (CD4 Molecule) • IL2 (Interleukin 2)
|
B2M mutation
4ms
Primary bone diffuse large B-cell lymphoma (PB-DLBCL): a distinct extranodal lymphoma of germinal centre origin, with a common EZB-like mutational profile and good prognosis. (PubMed, Histopathology)
This study comprehensively characterizes PB-DLBCL as a separate entity with distinct clinical and morpho-molecular features. These insights may aid in developing tailored therapeutic strategies and shed light on its pathogenesis.
Journal • IO biomarker
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TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • B2M (Beta-2-microglobulin)
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TP53 mutation • B2M mutation • BCL2 rearrangement • BCL6 translocation
5ms
Intracytoplasmatic BCMA Point Mutation and Teclistamab Resistance: Genomic Assessment of a Multidrug-Resistant Multiple Myeloma Patient (ASH 2023)
Here we present genetic profiling of a multi-refractory MM patient who relapsed to PIs, anti-BCMA (Teclistamab), and anti-GPRC5D (Talquetamab) BsAbs. However, the role of B2M alterations in disease progression and drug resistance needs to be elucidated. Predicting the biological impact based on 3D structural models remains speculative, thus, functional confirmation introducing the BCMA and B2M alterations in cell line models by genetic engineering is pending.
Clinical • IO biomarker
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CD8 (cluster of differentiation 8) • TNFRSF17 (TNF Receptor Superfamily Member 17) • B2M (Beta-2-microglobulin) • LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase)
|
B2M mutation
|
Talvey (talquetamab-tgvs) • Tecvayli (teclistamab)
5ms
Genomic, Transcriptional, and Immunological Validation of Distinct Molecular Subtypes of Classic Hodgkin Lymphoma through Tissue-Based and Noninvasive Methods (ASH 2023)
Collectively, these results serve to validate H1 and H2 as distinct cHL subtypes, to confirm the characteristic genotypes defining them, and recapitulate their distinctive associations with key clinical and pathological variables including age and EBV status. We further validate the subtypes using orthogonal methods revealing dominant cytokine driven signaling in H1. Conversely, H2 tumors, which largely lack B2M mutations, despite their lower mutational burden, are rather immunogenic triggering T-cell responses.
Tumor mutational burden • IO biomarker
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TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • KMT2D (Lysine Methyltransferase 2D) • B2M (Beta-2-microglobulin)
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TP53 mutation • TMB-H • TMB-L • B2M mutation
5ms
Multi-Dimensional Molecular and Tumor-Microenvironment Analysis of Classic Hodgkin Lymphoma (ASH 2023)
Conclusion Our multi-dimensional profiling approach enabled us to delineate molecular profiles of HRS cells that are linked to distinct TME patterns. These linkages have implications for current pathogenesis models, molecular subtyping of CHL, and identification of cellular vulnerabilities that might be therapeutically exploitable via targeting of HRS cell phenotypes and/or immune escape mechanisms.
PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1) • TNFRSF8 (TNF Receptor Superfamily Member 8) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • B2M (Beta-2-microglobulin) • PD-L2 (Programmed Cell Death 1 Ligand 2) • CD4 (CD4 Molecule) • TNFAIP3 (TNF Alpha Induced Protein 3) • GNA13 (G Protein Subunit Alpha 13) • BCL7A (BAF Chromatin Remodeling Complex Subunit BCL7A) • CD68 (CD68 Molecule) • SOCS1 (Suppressor Of Cytokine Signaling 1) • CD58 (CD58 Molecule) • FOXP3 (Forkhead Box P3) • STAT6 (Signal transducer and activator of transcription 6) • ZNF217 (Zinc Finger Protein 217) • H1-4 (H1.4 Linker Histone, Cluster Member) • TBL1XR1 (TBL1X Receptor 1)
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TNFRSF8 expression • B2M mutation • MHC-II expression • CD58 mutation • SPEN mutation
7ms
Concurrent predictors of an immune responsive tumor microenvironment within tumor mutational burden-high breast cancer. (PubMed, Front Oncol)
Along with MSI-H and PD-L1+, several biomarkers, including B2M mutation and CD274 amplification, may help predict ICI benefit amongst TMB-H tumors. Co-occurring biomarkers within TMB-H breast cancer warrant evaluation in larger cohorts for response or resistance to ICI to develop composite predictive biomarkers in MBC.
Journal • Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • B2M (Beta-2-microglobulin) • CDH1 (Cadherin 1)
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PD-L1 expression • TMB-H • MSI-H/dMMR • HER-2 negative • HER-2 mutation • TMB-L • PD-L1 amplification • B2M mutation • CDH1 mutation
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VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
7ms
Efficacy and safety of PD-1 monoclonal antibody plus rituximab in relapsed/refractory diffuse large B cell lymphoma patients. (PubMed, Eur J Haematol)
PD-1 mab combined with Rituximab could be a potential treatment option for r/r DLBCL with manageable safety profile.
Journal • PD(L)-1 Biomarker • IO biomarker
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B2M (Beta-2-microglobulin)
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B2M mutation
|
Rituxan (rituximab)
10ms
A PROSPECTIVE STUDY OF TARGETED SEQUENTIAL IMMUNOTHERAPY. IN PATIENTS WITH RELAPSED REFRACTORY PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA. (EHA 2023)
Treatment for rrPMBCL can include targeted sequential immunotherapy. If a PD1 tumor reduction regimen achieves PR or higher, patients should begin CART as soon as possible. B2M mutation-positive, SOCS1-positive patients can benefit from targeted sequential immunotherapy.
Clinical • PD(L)-1 Biomarker • IO biomarker
|
B2M (Beta-2-microglobulin) • SOCS1 (Suppressor Of Cytokine Signaling 1) • STAT6 (Signal transducer and activator of transcription 6)
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ERBB3 mutation • B2M mutation • SOCS1 mutation
12ms
Prevalence and Associations of Beta2-Microglobulin Mutations in MSI-H/dMMR Cancers. (PubMed, Oncologist)
In conclusion, patients carrying MSI-H/dMMR tumors with B2M mutation showed significantly higher TMB. Prescription of ICIs should be thoroughly evaluated for these patients.
Journal • Tumor mutational burden • MSi-H Biomarker • IO biomarker
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TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • B2M (Beta-2-microglobulin)
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TMB-H • MSI-H/dMMR • B2M mutation • B2M mutation + MSI-H/dMMR
1year
Tumor evolution and immune microenvironment dynamics define response to neoadjuvant treatment of esophageal adenocarcinoma (AACR 2023)
To characterize immune response we performed imaging mass cytometry (IMC) with a 18-marker panel on 26 samples from 9 REs and 16 samples from 6 NRs and T-cell receptor sequencing in 18 RE-samples and 9 NR-samples. We observed profound changes in mutation signatures over time, characterized by C>A transitions after exposure to neoadjuvant chemotherapy (FOLFOX), which is consistent with earlier observed oxaliplatin induced mutational signatures... Using a multi-timepoint approach, we integrated genetic analyses with transcriptomic analyses and analyses of the tumor immune microenvironment for a holistic understanding of treatment resistance. This study identifies profound transcriptional changes during treatment with limited evidence that clonal replacement is the cause, suggesting phenotypic plasticity as a mechanism for therapy resistance. The presence of immune escape, a less activated T-cell phenotype and a lack of clonal T-cell expansions in patients with poor clinical treatment response has high pharmacological relevance and could be exploited via combined immune-chemotherapy treatments.
Clinical • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • B2M (Beta-2-microglobulin)
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PD-L1 overexpression • B2M mutation
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5-fluorouracil • oxaliplatin • leucovorin calcium
1year
Primary cutaneous blastic marginal zone lymphoma: A comprehensive clinical, light microscopic, phenotypic and cytogenetic appraisal. (PubMed, Ann Diagn Pathol)
Blastic MZL is associated with a more aggressive clinical course. Even when there is disseminated disease patients while not always cured did not have a fatal course in this series. The light microscopic findings are reproducible. The background of MZL, identification of larger cells in significant numbers without a follicle center phenotype, at times expressing CD5 or CD23 with variable positivity for MUM1, BCL-2 and C-MYC and a high proliferation index define the pathology in most. Certain cytogenetic abnormalities and genetic mutations implicated in large cell transformation into a diffuse large B cell lymphoma are seen in blastic MZL with earlier biopsies prior to transformation potentially harboring at risk genetic mutations.
Journal • IO biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • B2M (Beta-2-microglobulin) • CD5 (CD5 Molecule) • IRF4 (Interferon regulatory factor 4) • FCER2 (Fc Fragment Of IgE Receptor II)
|
B2M mutation
1year
B2M mutation paves the way for immune tolerance in pathogenesis of Epstein-Barr virus positive diffuse large B-cell lymphomas. (PubMed, J Cancer)
These results suggest that the mutations of B2M could cause the disruption of the expression and functions of this important subunit of HLA, leading to decreased expression of HLA-I or HLA-II and subsequently to reduce T lymphocyte infiltration in tumor tissues. The consequence of this event lessens the recognition and elimination of EBV+ tumor cells by host immunity and paves the way for the host immune tolerance to EBV+ tumor cells by evading immune recognition and escaping the T lymphocyte killing.
Journal
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CD8 (cluster of differentiation 8) • B2M (Beta-2-microglobulin)
|
B2M mutation
1year
Exploring the Clinical Relevance of Beta-2-microglobulin in Colorectal Carcinoma: Immunohistochemistry May Serve as a Reliable Detection Method (USCAP 2023)
Our results suggest B2M IHC can likely serve as a reliable methodology in detecting B2M loss in CRCs. Our data also reaffirm literature reports that B2M loss characterizes a significant subset of MMR-deficient CRCs (41% in our series). As efforts are ongoing in further defining the clinical and biological relevance of B2M, especially with regard to the response to immunotherapy in MMR-deficient CRCs, B2M IHC may serve as a useful detection method in both clinical and research settings.
Clinical • IO biomarker
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MLH1 (MutL homolog 1) • B2M (Beta-2-microglobulin)
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B2M mutation
over1year
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
almost2years
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 • PD(L)-1 Biomarker • MSi-H 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
2years
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
over2years
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
over2years
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
|
B2M (Beta-2-microglobulin)
|
B2M mutation
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Keytruda (pembrolizumab) • Opdivo (nivolumab) • Yervoy (ipilimumab)
almost3years
[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
over3years
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) • CD79B (CD79b Molecule) • B2M (Beta-2-microglobulin) • PIM1 (Pim-1 Proto-Oncogene) • FOXO1 (Forkhead box O1)
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ARID1A mutation • MYD88 mutation • CD79B mutation • B2M mutation • PIM1 mutation
over3years
[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) • CD19 (CD19 Molecule) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • B2M (Beta-2-microglobulin) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • GZMA (Granzyme A)
|
PD-L1 overexpression • PD-L1 amplification • B2M mutation
over3years
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
|
MSI (Microsatellite instability) • B2M (Beta-2-microglobulin)
|
B2M mutation
over3years
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
|
KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • B2M (Beta-2-microglobulin)
|
KRAS mutation • MSI-H/dMMR • BRAF mutation • B2M mutation • TILs
almost4years
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)
|
MSI-H/dMMR • B2M mutation
almost4years
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)
|
TP53 mutation • B2M mutation
|
Rituxan (rituximab)
almost4years
[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)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • B2M mutation • EGFR L858R + EGFR exon 19 deletion
4years
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
|
BRAF (B-raf proto-oncogene) • B2M (Beta-2-microglobulin)
|
BRAF V600 • B2M mutation
|
Keytruda (pembrolizumab) • Opdivo (nivolumab) • Mekinist (trametinib) • Tafinlar (dabrafenib)