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    GENE:

    MLH1 (MutL homolog 1)

    i
    2d
    Role of DNA methylation and non‑coding RNAs expression in pathogenesis, detection, prognosis, and therapy‑resistant ovarian carcinoma (Review). (PubMed, Mol Med Rep)
    The present review focused on the role of DNA methylation and non‑coding RNA expression in the development of ovarian carcinomas and their association with diagnosis, prognosis, and the resistance of cancer cells to radiotherapy and chemotherapy. The present review considered the transition from the DNA structure to the RNA expression in ovarian carcinoma.
    Review • Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    3d
    Combination Chemotherapy, Bevacizumab, and/or Atezolizumab in Treating Patients With Deficient DNA Mismatch Repair Metastatic Colorectal Cancer, the COMMIT Study (clinicaltrials.gov)
    P3, N=120, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended
    Trial suspension
    |
    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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    Avastin (bevacizumab) • Tecentriq (atezolizumab) • oxaliplatin • Aybintio (bevacizumab biosimilar) • leucovorin calcium • Vegzelma (bevacizumab-adcd) • Avzivi (bevacizumab-tnjn) • fluorouracil topical
    3d
    Constitutional Epimutations: From Rare Events Toward Major Cancer Risk Factors? (PubMed, JCO Precis Oncol)
    In this review, we provide a summary of findings linking constitutional epimutations to cancer risk with emphasis on PCE. We also highlight challenges in detection of PCE exemplified by low-level mosaic epimutations in BRCA1 and indicate the need for further studies, hypothesizing that improved knowledge about PCE may add significantly to our understanding of cancer risk, carcinogenesis, and potentially development of other diseases as well.
    Review • Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2)
    6d
    Coexisting germline variants of MLH1 and MSH6 in a patient with Lynch syndrome who had uterine and ovarian cancer. (PubMed, Int Cancer Conf J)
    The use of an immune checkpoint inhibitor pembrolizumab resulted in durable partial response of metastatic lung tumors. This case reminds clinicians of the rare possibility of multiple germline variants in MMR genes in individuals with Lynch syndrome.
    Journal • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    |
    Keytruda (pembrolizumab)
    6d
    Analyzing pathogenic variants in mismatch repair genes: personalized prevention strategies for lynch syndrome in Chinese families. (PubMed, Front Med (Lausanne))
    Thus, 5-fluorouracil-based adjuvant chemotherapy is not recommended for patients with lynch syndrome. The novel stop gain mutant (NM_000251.2:c.1486delT:p.L496*) in MSH2 is deemed pathogenic for LS, and the mutant (NM_001258271.1:c.884 + 4A > G) in MLH1 has been further confirmed to be pathogenic. These findings expand the spectrum of mismatch repair gene variations in the ethnic group Han of China and reaffirm the importance of genetic testing for LS.
    Journal • Mismatch repair
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    MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2)
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    5-fluorouracil
    7d
    Expression patterns of mismatch repair proteins in cervical cancer uncover independent prognostic value of MSH-2. (PubMed, Int J Gynecol Cancer)
    MMR-D is rare in cervical cancer, yet low MSH-2 expression is an independent predictor of poor survival.
    Journal • Mismatch repair • Tumor mutational burden • IO biomarker
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    TMB (Tumor Mutational Burden) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • PMS2 (PMS1 protein homolog 2) • RAD50 (RAD50 Double Strand Break Repair Protein)
    9d
    Robotic Resection of Colonic Medullary Carcinoma: A Case Report. (PubMed, Cureus)
    No adjuvant therapy was recommended after a multidisciplinary review given the tumor's MMR deficiency and absence of regional lymph node metastasis. This report highlights the diagnostic challenges of MC and the potential benefits of a robotic approach for MC resections in an elderly patient.
    Journal
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    MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2)
    9d
    Integrating network pharmacology and experimental validation to uncover the synergistic effects of Huangqi ()-Ezhu () with 5-fluorouracil in colorectal cancer models. (PubMed, J Tradit Chin Med)
    HQEZ has synergistic effects on the anti-tumor activity of 5-FU in the treatment of colorectal cancer both in vivo and in vitro. The beneficial effect of HQEZ results from the inhibition of the drug sensitivity targets associated with 5-FU. The combination therapy of HQEZ with 5-FU or other chemotherapeutic drugs will also improve the anti-tumor efficacy of chemotherapy.
    Preclinical • Journal • BRCA Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • BRCA1 (Breast cancer 1, early onset) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • MLH1 (MutL homolog 1) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • ABCG2 (ATP Binding Cassette Subfamily G Member 2) • ABCC1 (ATP Binding Cassette Subfamily C Member 1) • TYMS (Thymidylate Synthetase) • MMP2 (Matrix metallopeptidase 2) • RRM1 (Ribonucleotide Reductase Catalytic Subunit M1) • PTGS2 (Prostaglandin-Endoperoxide Synthase 2) • TLR9 (Toll Like Receptor 9) • TLR4 (Toll Like Receptor 4) • MMP9 (Matrix metallopeptidase 9) • DPYD (Dihydropyrimidine Dehydrogenase) • PACERR (PTGS2 Antisense NFKB1 Complex-Mediated Expression Regulator RNA)
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    5-fluorouracil
    9d
    Genomic Signature for Initial Brain Metastasis Velocity (iBMV) in Non-Small-Cell Lung Cancer Patients: The Elusive Biomarker to Predict the Development of Brain Metastases? (PubMed, Cancers (Basel))
    Patients with a positive iBMV risk score were more likely to develop brain metastases. Validation of this signature could lead to a biomarker with the potential to guide treatment recommendations and surveillance schedules.
    Journal
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    BRAF (B-raf proto-oncogene) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • GNAQ (G Protein Subunit Alpha Q) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • CDK4 (Cyclin-dependent kinase 4) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • TSC1 (TSC complex subunit 1) • RAD51D (RAD51 paralog D) • ARAF (A-Raf Proto-Oncogene)
    11d
    Immunohistochemical insights into the pathogenesis of colonic sessile serrated lesions. (PubMed, Arch Clin Cases)
    SSLs are heterogeneous lesions, exhibiting a wide range of histological and molecular features. Using IHC might enhance diagnostic accuracy, particularly in lesions with ambiguous histological features, when dysplasia develops. Accurate identification of SSLs and understanding their molecular characteristics are crucial for assessing their malignant potential.
    Journal
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    TP53 (Tumor protein P53) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • MLH1 (MutL homolog 1) • CD44 (CD44 Molecule) • MUC2 (Mucin 2) • MUC5AC (Mucin 5AC) • MUC6 (Mucin 6)
    16d
    Lower degree of microsatellite instability in colorectal carcinomas from MSH6-associated Lynch syndrome patients. (PubMed, Mod Pathol)
    Future studies should carefully evaluate this possibility. If confirmed, these results would reinforce the notion of classifying LS as distinct syndromes associated with specific MMR genes.
    Journal • Microsatellite instability • IO biomarker
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    MSI (Microsatellite instability) • HLA-A (Major Histocompatibility Complex, Class I, A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • B2M (Beta-2-microglobulin)
    16d
    Study on the Application of MLPA Detection for Large Fragment Loss of Mismatch Repair Genes in Chinese HNPCC Families. (PubMed, Discov Med)
    Array-MLPA is a highly efficient and precise method for clinical screening and diagnosis of HNPCC. By using this method, we found that the HNPCC families carry deletions of MLH1 and MSH2 genes, which are the major germline genomic aberrations in the studied probands. Nevertheless, the deletion of the MSH6 gene is considered a rare occurrence in Chinese HNPCC families, according to our researche. Despite that, it is of clinical significance to screen and diagnose the HNPCC at the early phase by detecting the germline genomic large aberrations in MSH2/MLH1 genes.
    Journal • Mismatch repair
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    17d
    Wdr5-mediated H3K4 methylation facilitates HSPC development via maintenance of genomic stability in zebrafish. (PubMed, Proc Natl Acad Sci U S A)
    Subsequently, we found that DDR-associated genes, mutL homolog 1 and breast and ovarian cancer interacting helicase 1, are important to ensure HSPC survival, likely by stabilizing their genome. In summary, these findings reveal that Wdr5-mediated H3K4 methylation is essential for HSPC development through tight control of R-loop accumulation and DDR-associated program to ensure genomic stability and survival of proliferating HSPCs.
    Journal
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    MLH1 (MutL homolog 1) • WDR5 (WD Repeat Domain 5)
    18d
    Prevalence of Mismatch Repair Deficiency in Primary Prostate Cancer in a Large Prospective Cohort. (PubMed, Clin Cancer Res)
    In this nationwide prospective study, MMR deficiency was rare in primary, surgically treated prostate cancer. The low prevalence and the need for an internal positive control for this assay are feasibility concerns for unselected routine immunohistochemistry-based screening for MMR deficiency on limited tissue specimens, such as prostate biopsies.
    Journal • Mismatch repair • 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)
    18d
    MMR deficiency is frequent in colorectal carcinomas with diffuse SLFN11 immunostaining: clinicopathologic and molecular study of 31 cases identified among 3,300 tumors. (PubMed, J Pathol Clin Res)
    BRAF p.V600E mutation was found in 45% (9/20) of mismatch repair deficient, but only 1 of 11 proficient tumors. Colorectal carcinomas with diffuse SLFN11 positivity were often mismatch repair deficient tumors with their typical clinical, morphological, and molecular characteristics.
    Journal
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    BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • SLFN11 (Schlafen Family Member 11)
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    BRAF V600E • MSI-H/dMMR • BRAF V600
    19d
    Pathogenic germline variants in patients with early-onset colorectal cancer according to phenotype. (PubMed, Eur J Hum Genet)
    Phenotypic features should be taken into account for testing decision. Evaluating the cost-effectiveness of testing all CRC cases < 41 years, as well as how it aligns with the constraints of various healthcare systems, is warranted.
    Journal
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    TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • 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) • POLD1 (DNA Polymerase Delta 1) • EPCAM (Epithelial cell adhesion molecule) • MSH3 (MutS Homolog 3) • MUTYH (MutY homolog) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A)
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    MSI-H/dMMR
    23d
    Canadian consensus for the assessment and testing of Lynch syndrome. (PubMed, J Med Genet)
    This is the first comprehensive Canadian guideline for LS providing guidance to genetic specialists, laboratories, primary care providers and healthcare providers caring for patients with LS. It is endorsed by the Canadian College of Medical Genetics and the Canadian Association of Genetic Counsellors. The consensus statements are presented as a model for standard of care that improves equitable access to health services for LS across the country. Future work should include a national consensus on LS surveillance, with a goal to harmonise LS care across all provincial and territorial healthcare authorities.
    Journal
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    BRAF (B-raf proto-oncogene) • MLH1 (MutL homolog 1)
    24d
    Novel De Novo BRCA2 Variant in an Early-Onset Ovarian Cancer Reveals a Unique Tumor Evolution Pathway. (PubMed, Int J Mol Sci)
    Furthermore, ECM components, such as collagen isoforms, Fibrillin-1, EMILIN-1, Prolargin, and Lumican, were found to be highly expressed in the MLH1/PMS2-deficient tumor area, suggesting a connection between DNA repair deficiencies, ECM remodeling, and tumor progression. Thus, the identification of the BRCA2 variant sheds light on the poorly understood interplay between DNA repair deficiencies and ECM remodeling in OC, providing new insights into their dual role in shaping tumor evolution and suggesting potential targets for novel therapeutic strategies.
    Journal • BRCA Biomarker
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    BRCA2 (Breast cancer 2, early onset) • BCL6 (B-cell CLL/lymphoma 6) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2) • NOTCH2 (Notch 2) • KDM6A (Lysine Demethylase 6A) • CUX1 (cut like homeobox 1) • DRD (DNA Repair Deficiency) • FANCG (FA Complementation Group G) • LUM (Lumican)
    25d
    PhII Trial Panitumumab, Nivolumab, Ipilimumab in Kras/Nras/BRAF Wild-type MSS Refractory mCRC (clinicaltrials.gov)
    P2, N=56, Completed, UNC Lineberger Comprehensive Cancer Center | Active, not recruiting --> Completed
    Trial completion
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
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    KRAS wild-type • NRAS wild-type
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    Opdivo (nivolumab) • Yervoy (ipilimumab) • Vectibix (panitumumab)
    25d
    Researching the Effect of Aerobic Exercise on Cancer (clinicaltrials.gov)
    P=N/A, N=38, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting
    Enrollment closed
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule)
    25d
    Pathogenic germline variants in cancer predisposition genes in patients with multiple primary cancers in an Asian population and the role of extended panel genetic testing. (PubMed, ESMO Open)
    Patients with MPC were more likely to harbour a PGV. Extended testing improved PGV detection rates, particularly for less well-known cancer predisposition genes.
    Journal • BRCA Biomarker
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • TET2 (Tet Methylcytosine Dioxygenase 2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MBD4 (Methyl-CpG Binding Domain 4, DNA Glycosylase) • BARD1 (BRCA1 Associated RING Domain 1) • DDX41 (DEAD-Box Helicase 41) • FANCL (FA Complementation Group L) • CTNNA1 (Catenin Alpha 1) • RECQL4( RecQ Like Helicase 4) • SPINK1 (Serine peptidase inhibitor, kazal type 1) • CDKN1C (Cyclin Dependent Kinase Inhibitor 1C) • TNFRSF13B (TNF Receptor Superfamily Member 13B)
    25d
    Primary Endometrial Gastric (Gastrointestinal)-type Mucinous Adenocarcinoma: A Detailed Clinicopathologic and Molecular Analysis of 27 Cases. (PubMed, Am J Surg Pathol)
    Like the cervical counterpart, primary EmGA has a distinctive morphologic appearance, harbors frequent TP53 mutations, and can be associated with adverse outcomes despite low-grade morphology and/or low-stage at presentation. They may be represented in all 4 TCGA molecular groups.
    Journal • BRCA Biomarker
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    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) • CLDN18 (Claudin 18) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • SMAD4 (SMAD family member 4) • PMS2 (PMS1 protein homolog 2) • CDX2 (Caudal Type Homeobox 2) • MUC6 (Mucin 6)
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    TP53 mutation • MSI-H/dMMR • POLE mutation
    26d
    Rare pathogenic structural variants show potential to enhance prostate cancer germline testing for African men. (PubMed, Nat Commun)
    Notable African-specific loss-of-function gene candidates include DNA damage repair MLH1 and BARD1 and tumour suppressors FOXP1, WASF1 and RB1. Representing only a fraction of the vast African diaspora, this study raises considerations with respect to the contribution of kilo-to-mega-base rare variants to PCa pathogenicity and African-associated disparity.
    Journal
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    RB1 (RB Transcriptional Corepressor 1) • MLH1 (MutL homolog 1) • BARD1 (BRCA1 Associated RING Domain 1) • FOXP1 (Forkhead Box P1)
    27d
    Significantly increased load of hereditary cancer-linked germline variants in infertile men. (PubMed, Hum Reprod Open)
    Infertility affects about 7-10% of men worldwide. In this study, one in 15 men with spermatogenic failure carried germline LP/P variants in hereditary cancer genes. As exome sequencing is gradually entering the molecular diagnostics setup in andrology, analyzing hereditary cancer-linked variants in the workup of infertile men will offer additional clinical benefits. Male factor infertility is typically diagnosed in men in their 30s, often before the onset of cancer or its symptoms. Early knowledge of germline predisposition to cancer enables timely screening and multidisciplinary management options, potentially improving the prognosis. The study data provide support for the shared monogenic etiologies of hereditary cancer and spermatogenic failure.
    Journal • BRCA Biomarker
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    BRCA2 (Breast cancer 2, early onset) • NF1 (Neurofibromin 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • WT1 (WT1 Transcription Factor) • TSC1 (TSC complex subunit 1) • FANCM (FA Complementation Group M) • HOXB13 (Homeobox B13) • LZTR1 (Leucine Zipper Like Transcription Regulator 1) • PHOX2B (Paired Like Homeobox 2B)
    27d
    Are all mismatch repair deficient endometrial cancers created equal? A large, retrospective, tertiary center experience. (PubMed, Eur J Cancer)
    MLH1-hypermethylated MMRd ECs display more aggressive clinicopathologic features compared to the other MMRd subgroups. However, although a suggestive trend toward poorer EFS was observed in the hypermethylated subset, particularly in the advanced setting, no significant differences in prognosis were detected among the MMRd subtypes.
    Retrospective data • Journal • Mismatch repair
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    TP53 (Tumor protein P53) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
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    MSI-H/dMMR
    1m
    Feasibility Study: IGNITE-TX (Identifying Individuals for Genetic Testing & Treatment) Intervention (clinicaltrials.gov)
    P=N/A, N=205, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting
    Enrollment closed
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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) • EPCAM (Epithelial cell adhesion molecule)
    1m
    Microsatellite-high intrahepatic cholangiocarcinoma with favorable treatment outcome using pembrolizumab. (PubMed, Clin J Gastroenterol)
    In the present case, a 65-year-old man with intrahepatic cholangiocarcinoma and lymph node metastasis could not be treated with a combination of gemcitabine, CDDP, and S-1. MSI-H intrahepatic cholangiocarcinoma is extremely rare. However, because pembrolizumab is expected to be effective, CGP testing should be actively performed.
    Journal • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
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    MSI (Microsatellite instability) • MLH1 (MutL homolog 1)
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    MSI-H/dMMR
    |
    Keytruda (pembrolizumab) • gemcitabine
    1m
    A case of multiple advanced colon cancers with spontaneous regression of only one lesion after biopsy: a case report and literature review. (PubMed, Clin J Gastroenterol)
    The ascending colon lesion showed weak positivity for MLH1, positivity for MSH2 and MSH6, and negativity for PMS2, indicating MMR deficiency, whereas the transverse colon lesion showed positivity for all of them, indicating MMR-proficient tumor. This is the first case report of multiple advanced colon cancers, where only one lesion exhibited spontaneous regression after biopsy, suggesting a potential link between MMR deficiency and the spontaneous regression of colorectal cancer.
    Journal
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    1m
    A Phase Ib/II Clinical Study on AK112 Combined or Not Combined With AK119 in pMMR/MSS Colorectal Cancer (clinicaltrials.gov)
    P1/2, N=170, Recruiting, Akeso | Not yet recruiting --> Recruiting | N=72 --> 170 | Trial completion date: Jul 2025 --> Aug 2026 | Trial primary completion date: May 2024 --> May 2026
    Enrollment open • Enrollment change • Trial completion date • Trial primary completion date
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium • Yidafan (ivonescimab) • drebuxelimab (AK119)
    1m
    Prevalence of Constitutional Pathogenic Variant in a Cohort of 348 Patients With Multiple Primary Cancer Addressed in Oncogenetic Consultation. (PubMed, Mol Genet Genomic Med)
    Patients referred for oncogenetic testing with MPM are more likely to carry pathogenic variants in cancer predisposition genes than patients with a single primary cancer (p < 0.05), especially if the cancers are related to the same predisposition syndrome. If the cancers are unrelated, no statistical difference in comparison to the single-cancer population was observed. For these latter patients, we recommend using the specific criteria of each tumor to propose appropriate genetic testing.
    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) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • EPCAM (Epithelial cell adhesion molecule) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
    1m
    Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients (clinicaltrials.gov)
    P1/2, N=60, Recruiting, National Cancer Institute (NCI) | Active, not recruiting --> Recruiting | Trial primary completion date: Jul 2025 --> Mar 2025
    Enrollment open • 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)
    |
    BRAF mutation
    |
    NOUS-209
    1m
    Prolonged Low-Dose Chromium (VI) Exposure Induces Oxidative Stress, Apoptotic Genes and Epigenetic Modification of DNA Repair Genes in the Brain and Kidney of Swiss Albino Mice. (PubMed, J Appl Toxicol)
    Methylation-specific PCR revealed DNA hypermethylation as a factor in the transcriptional reduction of specific DNA repair genes in these tissues. This study denotes that long-term low-dose Cr (VI) exposure not only surges oxidative stress and changes histoarchitecture and gene expression but also results in epigenetic modifications via DNA hypermethylation, impacting organs like the brain and kidney.
    Preclinical • Journal
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    MLH1 (MutL homolog 1) • RAD51 (RAD51 Homolog A) • DNMT1 (DNA methyltransferase 1) • MUTYH (MutY homolog) • SIRT1 (Sirtuin 1) • CAT (Catalase)
    1m
    Testing a Combination of Vaccines for Cancer Prevention in Lynch Syndrome (clinicaltrials.gov)
    P2, N=186, Recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2027 --> Jan 2028 | Trial primary completion date: Feb 2027 --> Jul 2027
    Trial completion date • Trial primary completion date
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule)
    |
    Anktiva (nogapendekin alfa inbakicept-pmln) • Tri-Ad5
    1m
    Atorvastatin ± Aspirin in Lynch Syndrome Syndrome (clinicaltrials.gov)
    P1, N=46, Recruiting, Fox Chase Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025
    Trial completion date • Trial primary completion date
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule) • CASP3 (Caspase 3)
    |
    atorvastatin
    1m
    Obesity correlates to the microsatellite instability of endometrial cancer: A retrospective observational study. (PubMed, Semin Oncol)
    This study demonstrates a significant association between obesity and MSI in EC, particularly affecting MLH1 and PMS2 expression. The findings suggest that obesity may contribute to EC development also through MMR deficiency.
    Observational data • Retrospective data • Journal • Microsatellite instability
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    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    1m
    MLH1 Methylation Status and Microsatellite Instability in Patients with Colorectal Cancer. (PubMed, Genes (Basel))
    No differences were identified when analyzing specific methylation regions in relation to MSI. This study is the first to describe MSI frequency in Mexican patients regardless of age.
    Journal • Microsatellite instability • MSi-H Biomarker
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1)
    |
    MSI-H/dMMR
    1m
    Integrated Analysis of Somatic DNA Variants and DNA Methylation of Tumor Suppressor Genes in Colorectal Cancer. (PubMed, Int J Mol Sci)
    Even in tumors where the loss of heterozygosity has been demonstrated by somatic variants alone, additional methylation of the same gene can occur. Our data demonstrate that somatic variants and hypermethylation of these tumor suppressor genes were considered independent, parallel events, not exclusive of each other or having one event affecting the other.
    Journal
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    TP53 (Tumor protein P53) • MLH1 (MutL homolog 1) • SMAD4 (SMAD family member 4) • APC (APC Regulator Of WNT Signaling Pathway)
    1m
    Development of Syngeneic Murine Glioma Models with Somatic Mismatch Repair Deficiency to Study Therapeutic Responses to Alkylating Agents and Immunotherapy. (PubMed, Curr Protoc)
    Temozolomide (TMZ), the standard frontline chemotherapeutic for GBM, is an alkylating agent that generates DNA O6-methylguanine (O6MeG) lesions..
    Preclinical • Journal • Mismatch repair • IO biomarker
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    MLH1 (MutL homolog 1)
    |
    temozolomide
    1m
    Considerations for hereditary breast and ovarian cancer syndrome molecular diagnosis: experience from the clinical practice. (PubMed, Breast Cancer Res Treat)
    Testing cancer susceptibility genes using an agnostic strategy confers a diagnostic benefit for hereditary cancer syndromes compared to phenotype-driven test, without adding complexity to the study. The analysis of healthy individuals with a family history of HBOC detects pathogenic variants in a cost-efficient percentage of cases, resulting in a good alternative strategy when the index case is unavailable.
    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) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
    1m
    Exosomal miR‑3681‑3p from M2‑polarized macrophages confers cisplatin resistance to gastric cancer cells by targeting MLH1. (PubMed, Mol Med Rep)
    By contrast, the overexpression of MLH1 effectively reversed the drug resistance of AGS cells to DDP caused by miR‑3681‑3p mimic transfection, as evidenced by a decrease in the IC50 value. In conclusion, exosomal miR‑3681‑3p from M2 macrophages may have a key role in conferring DDP resistance to gastric cancer by suppressing MLH1, offering a new therapeutic target for overcoming chemoresistance.
    Journal
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    MLH1 (MutL homolog 1) • CD163 (CD163 Molecule) • CD9 (CD9 Molecule) • MRC1 (Mannose Receptor C-Type 1) • TSG101 (Tumor Susceptibility 101)
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    cisplatin
    2ms
    Polyamine-Depleting Hydrogen-Bond Organic Frameworks Unleash Dendritic Cell and T Cell Vigor for Targeted CRISPR/Cas-Assisted Cancer Immunotherapy. (PubMed, Adv Mater)
    Once released, CRISPR-Cas9 knocks out the DNA mismatch repair (MMR)-related MLH1 gene, further elevating mutational burdens and generating neoantigens, ideal targets for DCs. This dual-action strategy not only corrects T-cell immunosuppression but also enhances DC efficacy, presenting a powerful approach for tumor immunotherapy.
    Journal • Tumor mutational burden • IO biomarker
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    TMB (Tumor Mutational Burden) • MLH1 (MutL homolog 1)
    2ms
    Clinicopathological and Immunohistochemical Risk Predictors for Ameloblastoma Recurrence. (PubMed, Head Neck Pathol)
    Radiographic appearance, treatment modality, and immunoexpression of mismatch repair proteins can be used as predictors of AMB recurrence.
    Observational data • Retrospective data • Journal
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    MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2)