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    GENE:

    MLH1 (MutL homolog 1)

    i
    Other names: MLH1, COCA2, FCC2, HNPCC, HNPCC2, MutL homolog 1
    4d
    Challenges in Diagnosing Isolated Rib Metastasis From Low-Grade Endometrial Carcinoma: Utility of USG-FNAC and Molecular Characterisation. (PubMed, Cytopathology)
    This case demonstrates the diagnostic value of USG-FNAC as a reliable and safe method for confirming metastasis in anatomically challenging locations. Additionally, it emphasises the importance of incorporating molecular profiling and recognising histological features such as squamous differentiation and MELF patterns as markers of aggressive behaviour in a subset of low-to-intermediate grade EC.
    Journal • IO biomarker
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    MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2)
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    MSI-H/dMMR • TP53 wild-type
    4d
    Sex differences in gastric cancer mutational burden reflect MLH1-associated epigenetic regulation. (PubMed, BMC Cancer)
    Together, our findings indicate that sex differences in mutation burden are linked to MLH1-associated epigenetic regulation, mismatch repair deficiency, and MSI/MMR-deficient tumor biology. These results highlight the importance of incorporating sex-specific molecular context into the interpretation of genomic biomarkers and support a more refined, biologically informed approach to precision oncology.
    Journal • Tumor mutational burden • IO biomarker
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    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1)
    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
    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
    |
    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
    Pancreatic Neuroendocrine Tumor in Lynch Syndrome: Expanding the Tumor Spectrum of Mismatch Repair Deficiency. (PubMed, Cureus)
    The patient was treated with capecitabine and temozolomide (CAPTEM) chemotherapy, pembrolizumab, long-acting repeatable octreotide (octreotide LAR), and diazoxide for hypoglycemia management. This case highlights the expanding phenotypic spectrum of Lynch syndrome and suggests that P-NETs may represent a rare but clinically significant manifestation. Early recognition of this association supports comprehensive genetic testing, enables the use of precision immunotherapy, and underscores the need for expanded surveillance strategies in patients with atypical tumor profiles.
    Journal • Mismatch repair • PD(L)-1 Biomarker • IO biomarker
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    MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2)
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    Keytruda (pembrolizumab) • temozolomide • capecitabine • octreotide acetate
    8d
    The germline MLH1 c.2054 C>T mutation disrupts DNA mismatch repair and is detectable by digital PCR. (PubMed, Cancer Lett)
    In addition to designing a novel digital PCR (dPCR) assay to rapidly detect MLH1 gene variants, we conducted in-depth analyses via molecular modeling, mutational signature analyses, and functional genetic assays to demonstrate that the MLH1 mutation results in a definitive MMR defect that increases cancer risk. This study emphasizes the need for improved diagnostic tools to identify pathogenic mutations in diverse populations.
    Journal • Mismatch repair
    |
    MLH1 (MutL homolog 1)
    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)
    11d
    Microsatellite status and minimal microsatellite shift in atypical endometrial hyperplasia and endometrial cancer: an analysis of 848 cases (PubMed, Zhonghua Bing Li Xue Za Zhi)
    Minimal microsatellite shift is commonly detected in MSI-H cases, and some cases are difficult to interpret due to their classification within the equivocal range. Increasing the number of microsatellite loci, combined with visualization graph comparison and integration of mismatch repair protein immunophenotype and histological features, can effectively improve the accuracy of MSI-H interpretation.
    Journal • MSi-H Biomarker
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    MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • PMS2 (PMS1 protein homolog 2)
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    MSI-H/dMMR • POLE mutation
    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
    14d
    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)
    14d
    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)