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    GENE:

    MSH2 (MutS Homolog 2)

    i
    Other names: MSH2, MutS Homolog 2, HMSH2, MutS (E. Coli) Homolog 2, MutS Homolog 2, Nonpolyposis Type 1, DNA Mismatch Repair Protein Msh2, MutS Protein Homolog 2, HNPCC1, HNPCC, LCFS2, COCA1, FCC1
    1d
    Mismatch repair deficiency and microsatellite instability in adrenocortical carcinoma. (PubMed, ESMO Open)
    DMMR occurs in a minority of ACC, often without MSI. Although Lynch syndrome accounts for a subset of cases, dMMR is not predictive of clinical features or ICI response. Nonetheless, MMR testing remains important for identifying individuals at hereditary cancer risk.
    Journal • Mismatch repair • Microsatellite instability • IO biomarker
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    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
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    MSI-H/dMMR
    1d
    LEAH: Cohort Evaluation of Body Fluids Early Detection of Cancer in High-risk Individuals (clinicaltrials.gov)
    P=N/A, N=5909, Not yet recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Initiation date: Jun 2025 --> Feb 2026
    Trial initiation date
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • POLE (DNA Polymerase Epsilon) • RUNX1 (RUNX Family Transcription Factor 1) • BAP1 (BRCA1 Associated Protein 1) • ETV6 (ETS Variant Transcription Factor 6) • MLH1 (MutL homolog 1) • CDK4 (Cyclin-dependent kinase 4) • MSH2 (MutS Homolog 2) • SMAD4 (SMAD family member 4) • CDH1 (Cadherin 1) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • POLD1 (DNA Polymerase Delta 1) • RAD51C (RAD51 paralog C) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • RAD51D (RAD51 paralog D) • DDX41 (DEAD-Box Helicase 41) • GATA2 (GATA Binding Protein 2) • DICER1 (Dicer 1 Ribonuclease III) • FLCN (Folliculin) • PRSS1 (Serine Protease 1) • SDHD (Succinate Dehydrogenase Complex Subunit D) • TXNIP (Thioredoxin Interacting Protein) • ANKRD26 (Ankyrin Repeat Domain Containing 26) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A) • HOXB13 (Homeobox B13)
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    TP53 mutation • PTEN deletion
    1d
    Immunotherapy response in microsatellite-stable poorly differentiated thyroid carcinoma with mismatch repair deficiency and high tumor mutational burden. (PubMed, Arch Endocrinol Metab)
    Based on these findings, pembrolizumab was initiated as first-line therapy...Our findings underscore that alternative biomarkers, such as somatic mutations in DNA repair genes including MSH2 and ATM, may predict unexpected responses to immune checkpoint blockade and inform therapeutic decisions, even in the context of MSS and borderline TMB. Broader implementation of molecular profiling is warranted to identify such patients.
    Journal • Mismatch repair • Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
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    PD-L1 expression • TMB-H • MSI-H/dMMR • ATM mutation
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    Keytruda (pembrolizumab)
    1d
    Machine Learning-Based Pathomics Signature in Predicting MSH2 Expression and Prognosis in Gastric Cancer. (PubMed, Clin Transl Gastroenterol)
    The machine learning-derived pathomics signature shows potential in predicting MSH2 expression. It can serve as a complementary research tool and provide clinically meaningful prognostic information for GC.
    Journal
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    MSH2 (MutS Homolog 2)
    1d
    Feasibility and impact of Lynch syndrome genetic testing in newly diagnosed colorectal cancer patients: a multicenter observational study in Greece. (PubMed, ESMO Gastrointest Oncol)
    Testing asymptomatic relatives identified two first-degree relatives with MSH2 mutations. These findings underscore the critical need for CRC-adapted preventive oncology and support the implementation of a national LS screening program in Greece, aligned with international guidelines.
    Observational data • Journal
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    MSI (Microsatellite instability) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
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    BRAF V600E • BRAF V600
    2d
    Metagenomic Evaluation of the Gut Microbiome in Patients With Lynch Syndrome and Other Hereditary Colonic Polyposis Syndromes (clinicaltrials.gov)
    P=N/A, N=77, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027
    Trial completion date • Trial primary completion date
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    STK11 (Serine/threonine kinase 11) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • SMAD4 (SMAD family member 4) • APC (APC Regulator Of WNT Signaling Pathway) • EPCAM (Epithelial cell adhesion molecule) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A)
    3d
    Exploring Microsatellite Instability in Endometrial Carcinomas: Clinicopathological Correlations and Clinical Implications-A Study from North India. (PubMed, Indian J Surg Oncol)
    MSI testing which has been used historically to identify patients with Lynch Syndrome and evaluate the severity and prognosis of MSI carcinomas now plays an important role in identifying patients who will benefit from targetable therapy. MMR study therefore recommended in all cases of endometrial carcinomas and detection of MMR proteins by IHC can indirectly reflect the status of MSI and is a reliable method of MSI detection.
    Journal • Microsatellite instability • IO biomarker
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    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
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    MSI-H/dMMR
    4d
    Radiation and TSR-042 (Dostarlimab) in People With Endometrial Cancer After They Receive Surgery (clinicaltrials.gov)
    P2, N=62, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027
    Trial completion date • Trial primary completion date • Checkpoint inhibition • Mismatch repair • MSI-H • dMMR
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    MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
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    MSI-H/dMMR • POLE mutation
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    Jemperli (dostarlimab-gxly)
    5d
    Neoadjuvant mFOLFOX6 Chemotherapy Combined With Anti-PD-1 Therapy in MSS/pMMR Locally Advanced Rectal Cancer (FIRM02 Study) (clinicaltrials.gov)
    P2, N=128, Not yet recruiting, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
    New P2 trial • pMMR
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
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    5-fluorouracil • oxaliplatin • leucovorin calcium • Hetronifly (serplulimab)
    5d
    Increased immunogenicity of hypermutated SB28 syngeneic glioblastoma is partially mediated by alterations in tumor chemokine expression. (PubMed, Neurooncol Adv)
    Clones were injected subcutaneously or intracranially with or without anti-PD-1/anti-CTLA4 and dexamethasone...Rather, rejection depended on increased secretion of pro-inflammatory chemokines. Msh2 and Mlh1 loss was not equivalent, suggesting that additional studies are needed to elucidate germline and somatic mismatch repair gene-specific immune alterations.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    TMB (Tumor Mutational Burden) • IFNG (Interferon, gamma) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • RAG1 (Recombination Activating 1)
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    TMB-H • MSI-H/dMMR • TMB-L
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    dexamethasone
    9d
    Genetic investigation of a Tunisian family with Lynch syndrome: a case report. (PubMed, Front Oncol)
    NGS analysis of the tumor tissue revealed a pathogenic BRCA2 variant (c.1813delA, p.Ile605TyrTer9), which provides a potential target for personalized therapy. This case report highlights the co-segregation of a rare pathogenic MSH2 variant in a Tunisian family and underscores its clinical implications for improving the management and surveillance of patients with Lynch syndrome.
    Journal • BRCA Biomarker • MSi-H Biomarker
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    BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • MUTYH (MutY homolog)
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    MSI-H/dMMR
    9d
    Results of a multigene panel testing approach targeting patients with suspected genetic predisposition to pancreatic ductal adenocarcinoma. (PubMed, Eur J Hum Genet)
    An exploratory approach consisting of unmasking the results of the NGS analysis of 123 « research » genes involved in the carcinogenesis was applied to the 447 patients tested negative for the different genes of our diagnostic panel. This approach failed to identify other susceptibility genes to pancreatic adenocarcinoma.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • APC (APC Regulator Of WNT Signaling Pathway) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)