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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
    6d
    Clinicopathologic Study of 39 Mismatch Repair-deficient Sarcomas Demonstrates Recurrent Histologic Patterns and Supports Universal Screening of Pleomorphic Rhabdomyosarcoma, Uterine Leiomyosarcoma, and Undifferentiated and Unclassified Sarcomas. (PubMed, Am J Surg Pathol)
    Histologic subtyping of unclassified sarcomas predicted prognosis and therapeutic response. We propose universal MMR IHC screening of (1) PRMS, (2) uterine LMS, (3) unclassified/UPS, and (4) any sarcoma in a patient with a personal or family history of Lynch syndrome.
    Journal • Mismatch repair • MSi-H Biomarker • IO biomarker • dMMR
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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
    6d
    KRAS/NRAS/BRAF Mutations and Mismatch Repair Deficiency in Patients with Early-Onset Colorectal Cancer: A Clinicopathological Analysis. (PubMed, Int J Surg Pathol)
    KRAS mutations were more frequent in dMMR tumors than in MMR-proficient tumors (63.8% vs 40.8%).ConclusionGenetic mutations in the RAS/RAF pathway and dMMR status are associated with distinct clinicopathological features in patients with early-onset CRC. dMMR is a potentially favorable prognostic marker.
    Journal • Mismatch repair
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
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    BRAF V600E • KRAS mutation • MSI-H/dMMR • BRAF mutation • NRAS mutation • BRAF V600 • KIT mutation • RAS mutation
    6d
    Phenotypic heterogeneity in carriers of a pathogenic MSH2 variant: implications for the diagnosis of Lynch syndrome. (PubMed, J Cancer Res Clin Oncol)
    ; In conclusion, Lynch syndrome tumor biology may be more heterogeneous than expected, and MSI and IHC should not be interpreted in isolation as exclusionary tests for an underlying germline MMR variant, but rather as markers of tumor-level biological consequences. Therefore, germline findings, tumor characteristics, and family history should be evaluated together in Lynch syndrome diagnosis and risk assessment.
    Journal • MSi-H Biomarker
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    MSI (Microsatellite instability) • MSH2 (MutS Homolog 2)
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    MSI-H/dMMR
    7d
    Avelumab and M6620 for the Treatment of DDR Deficient Metastatic or Unresectable Solid Tumors (clinicaltrials.gov)
    P1/2, N=23, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Jan 2027
    Trial completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CD4 (CD4 Molecule) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
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    Bavencio (avelumab) • berzosertib (M6620)
    7d
    NRG-GY025: Testing Nivolumab With or Without Ipilimumab in Deficient Mismatch Repair System (dMMR) Recurrent Endometrial Carcinoma (clinicaltrials.gov)
    P2, N=81, Recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2026 --> Jul 2032 | Trial primary completion date: Apr 2026 --> Jul 2032
    Trial completion date • Trial primary completion date • Mismatch repair • dMMR
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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
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    Opdivo (nivolumab) • Yervoy (ipilimumab) • ABP 206 (nivolumab biosimilar)
    7d
    NCI-2017-02296: Testing Olaparib in Patients With Advanced or Metastatic (Cancer That Has Spread) Bladder Cancer and Other Genitourinary Tumors With DNA-Repair Genetic Changes (clinicaltrials.gov)
    P2, N=60, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting
    Enrollment closed • Tumor mutational burden
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    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ABL1 (ABL proto-oncogene 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • NPM1 (Nucleophosmin 1) • POLE (DNA Polymerase Epsilon) • CCND1 (Cyclin D1) • BAP1 (BRCA1 Associated Protein 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • BRD4 (Bromodomain Containing 4) • DOT1L (DOT1 Like Histone Lysine Methyltransferase) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • FANCC (FA Complementation Group C)
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    PALB2 mutation • BRIP1 mutation
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    FoundationOne® CDx
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    Lynparza (olaparib)
    7d
    Protecting the health of donor-conceived offspring. (PubMed, Fam Cancer)
    Our recommendations include comprehensive genetic screening of all donors for actionable pathogenic variants, centralized registries linking donors to offspring, standardized protocols for updating families with new genetic information, and clear policies addressing donor anonymity in the genomic era. Implementation of these recommendations would significantly reduce preventable morbidity and mortality in donor-conceived individuals while respecting the rights of all parties involved.
    Journal
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    MSH2 (MutS Homolog 2)
    8d
    SCREEN-CUP: Menstrual Cup for Early Endometrial Cancer Detection in Lynch Syndrome (clinicaltrials.gov)
    P=N/A, N=25, Recruiting, Jessica D. St. Laurent, MD | Trial completion date: Sep 2026 --> Mar 2027 | Trial primary completion date: Sep 2026 --> Mar 2027
    Trial completion date • Trial primary completion date
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    8d
    The 'Prostate Cancer Screening for People at Genetic Risk of Aggressive Disease' (PATROL) study. (PubMed, BJU Int)
    If definitive treatment, study procedures will be collected for an additional 1 year. Long-term clinical outcomes will be collected annually until the study closes.
    Journal • BRCA Biomarker
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • HOXB13 (Homeobox B13)
    10d
    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)
    13d
    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
    13d
    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