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    GENE:

    MLH1 (MutL homolog 1)

    i
    Other names: MLH1, COCA2, FCC2, HNPCC, HNPCC2, MutL homolog 1
    4d
    CRISPR-mediated MLH1 disruption suppresses endometrial cancer growth via genomic instability induction and Wnt/β-catenin pathway inhibition. (PubMed, Folia Histochem Cytobiol)
    In EC cells with pre-existing MLH1 promoter methylation, MLH1-KD leads to MSI-H, enhances genomic instability, disrupts Wnt signaling, impairs cellular functions, and inhibits tumor growth, highlighting Wnt signaling and MSI-H as potential therapeutic targets in EC.
    Journal • MSi-H Biomarker
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    MSI (Microsatellite instability) • MLH1 (MutL homolog 1)
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    MSI-H/dMMR
    5d
    Pembrolizumab plus chemotherapy following lack of response to nivolumab-based therapy in MSI-High/dMMR advanced gastric cancer: a case report. (PubMed, Int Cancer Conf J)
    He subsequently received ramucirumab-based therapy, paclitaxel, and irinotecan...Pembrolizumab combined with capecitabine and oxaliplatin (CAPOX) was initiated as fifth-line therapy, resulting in notable regression of hepatic and nodal metastases. This case underscores the clinical importance of early MSI/MMR and genomic testing and suggests that re-administration of ICI plus chemotherapy may be a therapeutic option for selected patients with advanced gastric cancer who initially show limited response to ICI-based therapy.
    Journal • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • MSI-H • dMMR
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    HER-2 (Human epidermal growth factor receptor 2) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2)
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    MSI-H/dMMR • HER-2 negative
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    Keytruda (pembrolizumab) • Opdivo (nivolumab) • paclitaxel • capecitabine • Cyramza (ramucirumab) • oxaliplatin • irinotecan • Teysuno (gimeracil/oteracil/tegafur)
    7d
    A novel pathogenic APC variant identified in a Chinese pedigree with familial adenomatous polyposis. (PubMed, Front Genet)
    Our findings expand the spectrum of known APC variants and provide functional evidence for the pathogenicity of this variant. The rare co-occurrence of FAP and MSI-H in the proband enriches the molecular phenotypic spectrum of FAP-related tumors.
    Journal • MSi-H Biomarker
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    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2) • APC (APC Regulator Of WNT Signaling Pathway)
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    MSI-H/dMMR
    7d
    Diagnostic and Treatment Protocols for Peripheral Craniofacial Osteomas. (PubMed, J Craniofac Surg)
    Craniofacial osteomas are benign, slow-growing lesions most frequently found in the frontal bone and are more prevalent among females. The integration of imaging-based diagnosis, tailored surgical techniques, and selective genetic testing allows for accurate evaluation, effective treatment, and favorable postoperative outcomes.
    Journal
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    MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • EXT1 (Exostosin Glycosyltransferase 1)
    7d
    Efficacy of Immune Checkpoint Blockade in Advanced Upper Tract Urothelial Cancer With DNA Mismatch Repair Deficiency or Microsatellite Instability. (PubMed, JCO Precis Oncol)
    Our hypothesis-generating findings suggest that dMMR/MSI-H may serve as a biomarker of sensitivity to single-agent ICIs in advanced UTUC. External validation in larger, ideally prospective, studies is needed to confirm the effectiveness and durability of immune checkpoint blockade in this molecular subgroup.
    Retrospective data • Journal • Checkpoint inhibition • Mismatch repair • Microsatellite instability • MSi-H Biomarker • 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
    8d
    LEAH: Cohort Evaluation of Body Fluids Early Detection of Cancer in High-risk Individuals (clinicaltrials.gov)
    P=N/A, N=5909, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Not yet recruiting --> Recruiting
    Enrollment open
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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
    11d
    Genetic Predisposition to Pancreatic Cancer: A Systematic Review of Hereditary Syndromes and Familial Aggregation. (PubMed, Cancers (Basel))
    Identifying high-risk individuals is crucial for effective genetic counseling, testing, and potential screening programs to facilitate early diagnosis and improve outcomes. Future research should prioritize large prospective cohorts, screening programs, and the integration of emerging technologies, such as AI-assisted imaging.
    Review • 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) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
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    BRCA2 mutation • BRCA1 mutation • ATM mutation • STK11 mutation
    12d
    Synchronous triple cancers of synchronous endometrial and ovarian carcinoma complicated by renal cancer: a case report. (PubMed, Front Oncol)
    Notably, the presence of MMRd subtype in such synchronous tumors does not inherently indicate Lynch syndrome. This case underscores the importance of integrating molecular testing and clinical manifestations to accurately diagnose multiple primary malignancies and formulate tailored treatment plans.
    Journal
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    13d
    An intriguing journey into the hereditary syndromes predisposing to endometrial cancer: more than believed. (PubMed, Ther Adv Med Oncol)
    Genetics has been shown to affect several aspects of disease, including carcinogenesis, onset age, clinicopathological features, prognosis, and therapy response. In this review, we will investigate the impact of germline PVs in different genes on genetic susceptibility to the development of inherited EC, discussing the potential cancer risk in mutation carriers as well as prognostic implications and current therapeutic approaches, also evaluating the possibility of carrying out a more extensive routine genetic analysis for EC women, in order to increase the diagnostic power, improve prevention and surveillance strategies in genetically predisposed subjects, and implement tailored therapies.
    Review • Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • POLD1 (DNA Polymerase Delta 1) • MUTYH (MutY homolog)
    13d
    SCRT-CAPEOX-Serplulimab for MSS/pMMR Rectal Cancer With Oligometastases (clinicaltrials.gov)
    P2, N=51, Recruiting, First Affiliated Hospital of Zhejiang University | N=102 --> 51
    Enrollment change • Mismatch repair • pMMR
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
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    capecitabine • oxaliplatin • Hetronifly (serplulimab)
    13d
    Autophagy inhibition enhances PD-1 blockade efficacy in mismatch repair-proficient colorectal cancer. (PubMed, Cancer Genet)
    Our findings demonstrate that inhibiting autophagy improves the immunotherapeutic efficacy of PD-1/PD-L1 inhibitors in pMMR colorectal cancer. This study offers a new strategy to overcome resistance to PD-1/PD-L1 inhibitors in pMMR metastatic CRC by combining autophagy inhibition with immunotherapy.
    Journal • Mismatch repair • pMMR
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    CD8 (cluster of differentiation 8) • CCND1 (Cyclin D1) • MLH1 (MutL homolog 1) • TNFA (Tumor Necrosis Factor-Alpha) • CASP3 (Caspase 3) • CASP9 (Caspase 9)
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    MSI-H/dMMR
    14d
    Deficient Mismatch Repair Subtypes in Vietnamese Colorectal Cancer: Clinicopathologic Associations, Predictive Modeling, and IHC-PCR Concordance. (PubMed, Cancer Manag Res)
    dMMR status, especially dMutL, might be associated with clinicopathologic characteristics, which might support decision-making in clinical practice. These findings require validation in larger cohorts but may inform clinical screening practices in resource-limited settings.
    Journal • Mismatch repair • 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