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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
    2d
    Novel African American Colorectal Cancer MSH3 Variants Associate With Major Genomic Instability. (PubMed, Hum Mutat)
    While CRISPR-Cas9 knock-in of MSH3 variants (Exons 21, 22, and 23) in SW620 cells did not alter cell morphology, proliferation, protein localization, or MSH2 binding, we observed genetic changes that collectively underscore the bidirectional nature of STR instability in MSH3-deficient cells and reinforce this protein's pivotal role in suppressing slippage at longer repeat motifs. This study advances our understanding of how MSH3 deficiency contributes to genomic instability beyond canonically defined MSI loci, offering novel insights into the mutational landscapes of MMR-deficient tumors and how these MSH3 mutations can potentially contribute to the outcome of AA CRC patients.
    Journal • Tumor mutational burden
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    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MSH2 (MutS Homolog 2) • MSH3 (MutS Homolog 3) • CPEB1 (Cytoplasmic Polyadenylation Element Binding Protein 1) • ABCA1 (ATP Binding Cassette Subfamily A Member 1) • AKAP12 (A-Kinase Anchoring Protein 12) • ABCA13 (ATP Binding Cassette Subfamily A Member 13)
    5d
    Management of locally advanced lynch syndrome rectal cancer during pregnancy with neoadjuvant immunochemotherapy: a case report. (PubMed, Front Oncol)
    The patient subsequently underwent neoadjuvant chemoradiotherapy (50.4 Gy in 28 fractions) combined with two cycles of capecitabine plus oxaliplatin (CapeOx) and tislelizumab, achieving significant tumor regression (yT2N0M0). LS-associated rectal cancer during pregnancy requires individualized, multidisciplinary management. Medical termination followed by neoadjuvant immunochemoradiotherapy can optimize maternal outcomes while minimizing fetal and genetic risks.
    Journal
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
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    Tevimbra (tislelizumab-jsgr) • capecitabine • oxaliplatin
    5d
    Long-read sequencing bridges germline and somatic variant detection: a multi-modal approach for hereditary cancer diagnostics. (PubMed, Clin Transl Oncol)
    These findings highlight the complementary and non-redundant roles of somatic liquid biopsy and germline analyses. Rather than indicating diagnostic equivalence, the results show that each approach captures distinct but clinically relevant genomic information. The inclusion of ONT long-read sequencing may improve the characterization of inherited variants, particularly structural variants and phasing and may support more comprehensive risk assessment and therapeutic planning.
    Journal • BRCA Biomarker
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2)
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    TP53 mutation • PIK3CA mutation
    5d
    Identification of a novel intergenic EPCAM-MSH2 deletion causing EPCAM-associated Lynch syndrome by long-read nanopore sequencing. (PubMed, J Med Genet)
    The molecular phenotype closely mirrored the recognised mechanism for 3'-end EPCAM deletions, whereby aberrant EPCAM transcription interferes with MSH2 promoter regulation in a tissue-specific manner.These findings support reclassification of this variant to likely pathogenic and establish a diagnosis of EPCAM-associated Lynch syndrome. This report provides the first evidence that intergenic EPCAM-MSH2 deletions are associated with MSH2 epimutations and highlights the diagnostic utility of long-read sequencing for noncoding structural variants.
    Journal
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    MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule)
    6d
    Integrated tumor and germline profiling of lynch syndrome in a North Indian cohort. (PubMed, Front Oncol)
    Germline testing helps identify probands and FDRs who are healthy mutation carriers. Risk-reduction strategies for them can help reduce the risk of CRC in the Indian population.
    Journal
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    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    6d
    Germline Cancer Testing in Unselected Patients With Neuroendocrine Neoplasms: A Multi-center Prospective Study. (PubMed, Pancreas)
    Universal germline testing in unselected NEN patients identified clinically relevant PGVs in over 15% of cases. These findings support broader genetic testing approaches to guide treatment, enhance familial risk assessment, and inform cascade testing-regardless of traditional clinical selection criteria.
    Clinical • Journal
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog) • MITF (Melanocyte Inducing Transcription Factor)
    7d
    S2107: Testing the Addition of Nivolumab to Standard Treatment for Patients With Metastatic or Unresectable Colorectal Cancer That Have a BRAF Mutation (clinicaltrials.gov)
    P2, N=86, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2026 --> Jun 2027 | Trial primary completion date: Sep 2026 --> Feb 2026
    Trial completion date • Trial primary completion date
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    BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
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    BRAF V600E • BRAF V600
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    Opdivo (nivolumab) • Erbitux (cetuximab) • Braftovi (encorafenib) • ABP 206 (nivolumab biosimilar)
    7d
    Associations between molecular classification and response to intra-uterine levonorgestrel device therapy in patients with medically managed endometrial cancer and endometrial intra-epithelial neoplasia: a multi-center Endometrial Cancer Molecularly Targeted Therapy (ECMT2) Consortium study. (PubMed, Int J Gynecol Cancer)
    The complete response to levonorgestrel intra-uterine device therapy was lower than expected for endometrial intra-epithelial neoplasia. Response rates varied by molecular classification, with worse outcomes observed in deficient mismatch repair and p53 abnormal sub-types. Although limited by sample size, these findings suggest that levonorgestrel intra-uterine device therapy may not be sufficient for all molecular sub-groups.
    Journal
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    TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
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    MSI-H/dMMR • TP53 wild-type • POLE mutation
    7d
    Case Report: gastric signet-ring-cell adenocarcinoma in a young adult with tracheoesophageal fistula/esophageal atresia and complex gastrointestinal history. (PubMed, Front Oncol)
    This case highlights the interplay of congenital foregut anomalies, chronic inflammation, and SRC development, and underscores the critical importance of meticulous biopsy handling and personalized endoscopic care. Tailored surveillance may be appropriate in select early-stage SRC cases where localization is uncertain and imaging is negative.
    Journal
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    TP53 (Tumor protein P53) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1) • CTNNA1 (Catenin Alpha 1)
    7d
    Communication With Clinicians and Relatives About Cascade Genetic Testing in Cancer Patients With Germline Pathogenic Variants. (PubMed, JCO Precis Oncol)
    Patients with cancer are motivated to communicate PV results to relatives. However, few clinicians are involved and relatives' testing remains low. Novel care delivery models are needed to advance cascade testing and precision risk reduction.
    Journal • BRCA Biomarker
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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) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • SMAD4 (SMAD family member 4) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • EPCAM (Epithelial cell adhesion molecule) • BARD1 (BRCA1 Associated RING Domain 1) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A)
    8d
    Pathogenic Germline Variants in a Racially Diverse Real-World Cohort of Patients With Prostate Cancer. (PubMed, J Natl Compr Canc Netw)
    These data support NCCN Guideline-recommended universal genetic testing for patients with aggressive PCa.
    Journal • Real-world evidence • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2)
    12d
    Lynch syndrome with MLH1 germline variant in an extended family: a case report. (PubMed, Open Life Sci)
    Based on the clinical, pathological, and genetic findings, the extended family was diagnosed with LS. Taken together, MLH1 c.1652A>C (p.N551T) variant may contribute to carcinogenesis, and its co-segregation with LS in this family provides supportive evidence for its potential pathogenicity.
    Journal
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)