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    GENE:

    MLH1 (MutL homolog 1)

    i
    Other names: MLH1, COCA2, FCC2, HNPCC, HNPCC2, MutL homolog 1
    2ms
    Testing Immunotherapy (Atezolizumab) With or Without Chemotherapy in Locoregional MSI-H/dMMR Gastric and Gastroesophageal Junction (GEJ) Cancer (clinicaltrials.gov)
    P2, N=2, Active, not recruiting, National Cancer Institute (NCI) | N=240 --> 2 | Trial completion date: Oct 2027 --> Jun 2027 | Trial primary completion date: Oct 2027 --> Jan 2026
    Enrollment change • Trial completion date • Trial primary completion date • MSI-H • 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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    Tecentriq (atezolizumab) • docetaxel • capecitabine • oxaliplatin • leucovorin calcium • fluorouracil topical
    2ms
    Metachronous Colorectal Carcinomas and Pancreatic Metastasis in Clinically Suspected Lynch Syndrome: An 18-Year Oncologic Course. (PubMed, Cureus)
    The findings favored metastatic colorectal carcinoma involving the pancreas in the setting of clinically suspected Lynch syndrome. This case emphasizes the importance of clinicopathologic correlation, cautious interpretation of MMR deficiency, and long-term multidisciplinary surveillance.
    Journal
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    2ms
    Anti-Hu-Associated Paraneoplastic Myeloneuropathy as the Initial Presentation of Early-Onset Colon Adenocarcinoma. (PubMed, ACG Case Rep J)
    Postoperative circulating tumor DNA was negative, and the patient was placed on active surveillance; however, neurological symptoms persisted, and immunomodulatory therapy access was initially limited. This case highlights a rare association between anti-Hu-associated myeloneuropathy and early-onset colon cancer and underscores the importance of malignancy evaluation in unexplained sensory neuronopathy.
    Journal
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    BRAF (B-raf proto-oncogene) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase)
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    MSI-H/dMMR
    2ms
    Differences in Cascade Genetic Testing Among Families With Hereditary Cancer Risk. (PubMed, JAMA Netw Open)
    In this retrospective cross-sectional study, cascade testing was underused, especially among specific demographic groups, with clinical and cultural factors appearing to play a larger role than financial barriers. These findings may guide efforts to address barriers preventing wider uptake of cascade testing and improve cancer prevention efforts, particularly among racial and ethnic minority groups.
    Retrospective data • Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • EPCAM (Epithelial cell adhesion molecule)
    2ms
    Superficial serrated adenoma: a clinicopathological analysis of ten cases (PubMed, Zhonghua Bing Li Xue Za Zhi)
    Understanding its histological features and immunohistochemical profile facilitates its diagnosis and differential diagnosis, including CK20 positivity and Ki-67 negativity in the superficial layer, and high Ki-67 expression with negative CK20 staining in the deep layer. KRAS gene mutation is also an important diagnostic feature.
    Journal
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PMS2 (PMS1 protein homolog 2) • KRT20 (Keratin 20)
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    KRAS mutation • BRAF mutation
    2ms
    Relationship between MLH1, MSH2, MSH6, and PMS2 protein expression status and clinicopathological characteristics in colorectal cancer tissues. (PubMed, Front Med (Lausanne))
    These findings support the value of routine IHC-based MMR testing in CRC patients. However, confirmatory molecular testing (e.g., MSI analysis, BRAF V600E mutation, MLH1 promoter methylation, or germline sequencing) is necessary to differentiate sporadic from Lynch syndrome-associated dMMR cases and to fully guide Lynch syndrome screening and immunotherapy decisions.
    Journal • IO biomarker
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    BRAF (B-raf proto-oncogene) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
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    BRAF V600E • MSI-H/dMMR • BRAF V600
    2ms
    Mismatch repair protein deficiency (MMRd) and high microsatellite instability (MSI-H) in gastrointestinal stromal tumour (GIST) - a case report and review of the literature of this exceedingly rare phenotype. (PubMed, Virchows Arch)
    MSI testing by MSI PCR, however, showed a microsatellite stable result. This highlights how MSI PCR may not be sufficiently sensitive in detecting MSI-H status in tumour types outside of colorectal carcinomas.
    Journal • Mismatch repair • Tumor mutational burden • Microsatellite instability • MSi-H Biomarker • MSI-H • dMMR
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    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2) • ANO1 (Anoctamin 1)
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    MSI-H/dMMR
    2ms
    Machine Learning Algorithm for the Detection of Tumor Microsatellite Instability Based on Multiomics Biomarkers. (PubMed, JCO Clin Cancer Inform)
    Our ML approach accurately predicted MSI status in colorectal and uterine cancers using multiomics data derived from NGS, without relying on direct microsatellite sequencing. The ability to identify MSI-high tumors among indeterminate cases demonstrates potential to improve diagnostic precision and ensures timely access to immunotherapy for patients with MSI-high disease.
    Journal • Tumor mutational burden • Microsatellite instability • MSi-H Biomarker • IO biomarker
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    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2)
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    MSI-H/dMMR
    2ms
    Spontaneous Regression of Poorly Differentiated Carcinoma in the Transverse Colon with Deficient Mismatch Repair: A Case Report and Review. (PubMed, Surg Case Rep)
    We report an extremely rare case of SR of poorly differentiated CRC with dMMR and marked TILs. Enhanced tumor immunogenicity associated with dMMR and immune activation may contribute to CRC regression.
    Journal • Mismatch repair • MSi-H Biomarker • dMMR
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    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2) • CDX2 (Caudal Type Homeobox 2)
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    MSI-H/dMMR
    2ms
    Frequency of germline pathogenic variants in breast cancer predisposing genes in a national cohort of young women with breast cancer. (PubMed, Br J Cancer)
    Overall, 18.6% of women with young breast cancer had PVs in 18 genes tested, including 6.8% in a gene other than BRCA1 or BRCA2. Study results suggest that genetic testing should be offered to all women diagnosed breast cancer at the age of 40 or younger.
    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) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • EPCAM (Epithelial cell adhesion molecule) • BARD1 (BRCA1 Associated RING Domain 1)
    2ms
    SMT-SL: Determining the Prevalence of Muir-Torre Syndrome in Patients With Lynch Syndrome (clinicaltrials.gov)
    P=N/A, N=150, Recruiting, Centre Hospitalier Universitaire de Nīmes | Not yet recruiting --> Recruiting | Initiation date: Dec 2025 --> Mar 2026
    Enrollment open • Trial initiation date
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    2ms
    Mismatch repair protein "nonclassic expression loss" pattern in colorectal cancer: an important staining pattern that is not well understood. (PubMed, Am J Clin Pathol)
    Microsatellite instability high status (30.77%) and Lynch syndrome (3.85%) can occur in patients with only nonclassic loss of MMR proteins (without the B pattern). It is necessary to deepen our understanding of nonclassical MMR expression patterns to avoid missing patients with microsatellite instability high status and Lynch syndrome.
    Retrospective data • Journal • Mismatch repair • MSi-H Biomarker
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    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • PMS2 (PMS1 protein homolog 2)
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    MSI-H/dMMR