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    GENE:

    MLH1 (MutL homolog 1)

    i
    Other names: MLH1, COCA2, FCC2, HNPCC, HNPCC2, MutL homolog 1
    1d
    A case of familial adenomatous polyposis in an adult male with Lynch-like syndrome (PubMed, Zhonghua Wei Chang Wai Ke Za Zhi)
    The patient underwent laparoscopic total colectomy with abdominoperineal resection and end ileostomy, then received 4 cycles adjuvant chemotherapy of oxaliplatin with capecitabine. This patient was followed up to April 2024 and performed well without abnormalities in serum cancer biomarkers and radiological examinations.
    Journal • Tumor mutational burden
    |
    KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • MLH1 (MutL homolog 1) • PTCH1 (Patched 1)
    |
    KRAS mutation • TMB-H • PIK3CA mutation • PTCH1 mutation • AKT1 mutation
    |
    capecitabine • oxaliplatin
    1d
    Multi-ethnic heterozygote frequencies of cancer susceptibility genes to inform counseling of reproductive risk. (PubMed, Genet Med)
    Heterozygote frequency estimates for AD CPGs that cause AR disease provides information to facilitate discussions regarding reproductive risk. Future studies are needed to assess whether utilization of these data will influence couples' reproductive risk planning.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • SDHD (Succinate Dehydrogenase Complex Subunit D) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
    3d
    Recurrent GRHL fusions in a subset of sebaceoma: microscopic and molecular characterisation of eight cases. (PubMed, Histopathology)
    In conclusion, we report recurrent fusions of the GRHL genes in a distinctive subset of sebaceomas harbouring infundibulocystic differentiation, a frequent organoid growth pattern and lack of mismatch repair deficiency.
    Journal
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    AR (Androgen receptor) • BCL6 (B-cell CLL/lymphoma 6) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • BCOR (BCL6 Corepressor) • TP63 (Tumor protein 63)
    |
    AR expression • MSH6 expression
    4d
    High Rates of Germline Pathogenic Variants in Somali Patients with Ovarian Cancer. (PubMed, Gynecol Oncol Rep)
    Comprehensive genomic profiling and community-based research are essential to address these disparities and improve cancer care for this underserved population. Larger studies are needed to validate these findings and to develop tailored interventions that enhance the prevention, diagnosis, treatment, and prognosis of ovarian cancer in Somali women.
    Journal • BRCA Biomarker
    |
    BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)
    |
    BRIP1 mutation
    5d
    The impact of preoperative treatment on mismatch repair protein and HER2 expression in colorectal cancer: an analysis of paired samples. (PubMed, BMC Cancer)
    PT is associated with a reduction in MMR expression, notably for the MSH2 protein, while it does not appear to influence HER2 expression.
    Retrospective data • Journal • Mismatch repair
    |
    HER-2 (Human epidermal growth factor receptor 2) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    |
    MSI-H/dMMR • HER-2 overexpression • HER-2 expression • MSH6 expression
    |
    5-fluorouracil • capecitabine
    5d
    Reclassification of Two MLH1 Variants of Uncertain Significance Utilizing Clinical and Functional Data. (PubMed, Mol Genet Genomic Med)
    By applying all collected data and functional results we propose to reclassify the c.696_698del, p.(Cys233del) and the c.1919C > G, p.(Pro640Arg) variants as likely pathogenic (class 4) using MMR gene-specific ACMG/AMP guidelines. Consequently, the two MLH1 variants can now be used for risk assessment of variant carriers, while family members without the variants can be excluded from intensified cancer surveillance and follow population recommendations.
    Journal
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    MLH1 (MutL homolog 1)
    6d
    Mainstreaming cancer genetics: feasibility of an advanced nurse practitioner-led service diagnosing Lynch syndrome from colorectal cancer in Ireland. (PubMed, Fam Cancer)
    Successful downstream delivery of clinical services, however, requires appropriate subsequent management, in a resource-limited environment. Our institutional experience demonstrates the feasibility, efficiency, and effectiveness of an ANP-led mainstreaming model of care for hereditary colorectal cancer.
    Journal • Metastases
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    BRAF (B-raf proto-oncogene) • MLH1 (MutL homolog 1)
    |
    MSI-H/dMMR • BRAF V600
    6d
    Mismatch Repair (MMR) and Homologous Recombination (HR) Deficiency: Real-Life Applications of biomarkers for complementary approaches in Epithelial Ovarian Cancer (AIOM 2024)
    HRD genomic instability tests and multigene panel assessments serve as synergistic tools in EOC clinical settings, proving essential for identifying patients likely to benefit from PARPi therapy. These tools also enhance the detection of HRR and MMR gene variants, aiding in preventive care. Further investigations into the genetic profiles of HRD-negative tumors are crucial for advancing cancer risk management and developing novel therapeutic avenues.
    Clinical • Mismatch repair • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MUTYH (MutY homolog)
    |
    BRCA2 mutation • BRCA1 mutation • HRD • BRCA wild-type
    |
    Myriad myChoice® CDx
    7d
    Advantages of next-generation sequencing (NGS) in the molecular classifi cation of endometrial carcinomas - our experience with 270 cases. (PubMed, Ceska Gynekol)
    In comparison with recommended diagnostic algorithms, NGS provides a more reliable classification of EC into particular molecular subgroups. Furthermore, NGS reveals the complex molecular genetic background in individual ECs, which is especially significant within ECs with no specific molecular profile. These data can serve as a springboard for the research of therapeutic programs committed to targeted therapy in this type of tumor.
    Journal • Next-generation sequencing • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PMS2 (PMS1 protein homolog 2) • BCOR (BCL6 Corepressor) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • POLD1 (DNA Polymerase Delta 1)
    |
    TP53 mutation • PIK3CA mutation • PTEN mutation • POLE mutation
    7d
    The guidelines for clinical practice for carriers of germline mutations in the Lynch syndrome predisposition genes MLH1, MSH2, MSH6, PMS2 and large deletions of EPCAM (4.2024). (PubMed, Klin Onkol)
    The drafting of the guidelines was organized by the Oncogenetics Working Group of the Society for Medical Genetics and Genomics of J. E. Purkyně Czech Medical Society, in cooperation with representatives of oncology, oncogynecology, and gastroenterology. The guidelines are based on the current recommendations of the National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO) and take into account the capacity of the Czech healthcare system.
    Clinical guideline • Journal
    |
    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • EPCAM (Epithelial cell adhesion molecule)
    |
    MSH2 mutation • PMS2 mutation • MSH6 deletion
    7d
    Germline mismatch repair gene mutations in children with tumors: a case series from two centers. (PubMed, Transl Pediatr)
    A better diagnostic approach is to perform genetic testing to rule out the risk as early as possible when a newborn presents with cafe-au-lait spots, which are a typical feature of hereditary syndromes. Therefore, it is important to use germline genetic testing, combined with clinical phenotypic observation, to establish a diagnosis of a cancer susceptibility syndrome caused by an MMR gene mutation.
    Journal • Mismatch repair
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    NF1 (Neurofibromin 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    MSH6 mutation • MSH2 mutation • MLH1 mutation
    8d
    Modeling adenoma-carcinoma progression from a single MLH1-knockout cell via colon organoids. (PubMed, Nat Cancer)
    No abstract available
    Journal
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    MLH1 (MutL homolog 1)
    8d
    Characteristics of Cancer in Subjects Carrying Lynch Syndrome-Associated Gene Variants in Taiwanese Population: A Hospital-Based Study in Taiwan. (PubMed, Cancers (Basel))
    The apparent under diagnosis of LS highlights the urgent need for enhanced surveillance and genetic counseling in this demographic. Our findings suggest that adjustments in the current screening protocols may be warranted to better identify and manage at-risk individuals.
    Journal
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    8d
    Genomic alterations associated with early-stage disease and early recurrence in patients with colorectal cancer. (PubMed, Oncologist)
    Early-stage CRC patients can have distinct genomic profiles and CGP in this population can help expand access to targeted therapies.
    Journal • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker
    |
    BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • 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) • RNF43 (Ring Finger Protein 43)
    |
    BRAF V600E • MSI-H/dMMR • BRAF V600 • RNF43 mutation
    |
    FoundationOne® CDx
    10d
    Performance of oncoReveal MLH1 and MGMT Methylation Panel from Pillar Bioscience (AMP 2024)
    This study demonstrates that oncoReveal MLH1 and MGMT Methylation Panel performed very well against comparator methods. The performance characteristics and workflow benefits are suitable for clinical testing.
    MGMT (6-O-methylguanine-DNA methyltransferase) • MLH1 (MutL homolog 1)
    |
    ONCO/Reveal™ Essential MPN Panel
    10d
    Diagnostic and Clinical Utility of OncoScan Microarray and NGS-Based Sequencing in Pediatric Solid Tumors: Children's Mercy Hospital Experience (AMP 2024)
    OS+ is a reliable test to identify clinically relevant genomic alterations, cnLOH, and several hotspot mutations in pediatric FFPE solid tumor specimens. WGS/WES significantly increases the yield of actionable somatic mutations and cancer-predisposing germline variants. The cost, turnaround time, and tumor percentage in the specimen make OS+ followed by WES principal tests for pediatric solid tumor analysis at our institution.
    Clinical • Next-generation sequencing
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NF1 (Neurofibromin 1) • MLH1 (MutL homolog 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • H3-3A (H3.3 Histone A)
    |
    TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • PIK3CA mutation • BRAF V600 • PTEN mutation • BRAF fusion
    |
    OncoScan™ CNV Assay
    10d
    Pembrolizumab Before Surgery for the Treatment of Mismatch Repair Deficient Locally Advanced Solid Cancers (clinicaltrials.gov)
    P2, N=35, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed
    Trial completion
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    MSI-H/dMMR
    |
    Keytruda (pembrolizumab)
    11d
    Radiation and TSR-042 (Dostarlimab) in People With Endometrial Cancer After They Receive Surgery (clinicaltrials.gov)
    P2, N=62, Recruiting, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Recruiting | N=31 --> 62 | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2025 --> Feb 2026
    Enrollment open • Enrollment change • Trial completion date • Trial primary completion date • Checkpoint inhibition • Mismatch repair • Surgery • Checkpoint block • Metastases
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    MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    MSI-H/dMMR • POLE mutation
    |
    Jemperli (dostarlimab-gxly)
    11d
    Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients (clinicaltrials.gov)
    P1/2, N=60, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    BRAF mutation • MSH2 mutation • MLH1 mutation • PMS2 mutation
    |
    NOUS-209
    13d
    A Phase 1/2 Study to Evaluate the Safety and Efficacy of MK-2870 Monotherapy or in Combination With Other Anticancer Agents in Gastrointestinal Cancers (ChiCTR2400089007)
    P2, N=130, Not yet recruiting, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Union Hospital, Tongji Medical College, Huazhong University of
    New P2 trial • Combination therapy
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRCA (Breast cancer early onset) • CD4 (CD4 Molecule)
    |
    MSI-H/dMMR • BRCA mutation • MSH6 expression
    |
    FoundationOne® CDx
    |
    5-fluorouracil • sacituzumab tirumotecan (MK-2870)
    15d
    A Phase 2 Study of Mirvetuximab Soravtansine (IMGN853) and Pembrolizumab in Endometrial Cancer (EC) (clinicaltrials.gov)
    P2, N=18, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Aug 2028 --> May 2027 | Trial primary completion date: Aug 2025 --> Jun 2024
    Trial completion date • Trial primary completion date • Combination therapy
    |
    FOLR1 ( Folate receptor alpha ) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    MSH6 expression
    |
    Keytruda (pembrolizumab) • Elahere (mirvetuximab soravtansine-gynx)
    15d
    Fecal Microbiota Transplant and Re-introduction of Anti-PD-1 Therapy (Pembrolizumab or Nivolumab) for the Treatment of Metastatic Colorectal Cancer in Anti-PD-1 Non-responders (clinicaltrials.gov)
    P2, N=15, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CEACAM5 (CEA Cell Adhesion Molecule 5)
    |
    MSI-H/dMMR
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab)
    16d
    PancreasScan: Pancreatic Cancer Screening for At-risk Individuals (clinicaltrials.gov)
    P=N/A, N=1395, Recruiting, Beth Israel Deaconess Medical Center | N=500 --> 1395 | Trial completion date: Mar 2028 --> Dec 2032 | Trial primary completion date: Mar 2027 --> Dec 2032
    Enrollment change • Trial completion date • Trial primary completion date
    |
    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) • BRCA (Breast cancer early onset) • EPCAM (Epithelial cell adhesion molecule) • PRSS1 (Serine Protease 1)
    |
    BRCA2 mutation • BRCA1 mutation • PALB2 mutation • CDKN2A mutation • MLH1 mutation • PMS2 mutation • BRCA mutation
    17d
    High risk of multiple gastric cancers in Japanese individuals with Lynch syndrome. (PubMed, Ann Gastroenterol Surg)
    Notably, the cumulative risk of individuals with LS developing metachronous and/or synchronous GCs at 0, 10 and 20 y after initial diagnosis of GC was 26.7%, 40.7%, and 59.4%, respectively. Due to a higher risk of developing multiple GCs, intensive surveillance might be especially recommended for Japanese individuals with LS associated initial GC.
    Journal
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    17d
    Molecular Classification of Endometrial Cancers Using an Integrative DNA Sequencing Panel. (PubMed, J Surg Oncol)
    Our panel can classify ECs into four subgroups through a simplified process and can be implemented reflexively in clinical practice.
    Journal
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    TP53 (Tumor protein P53) • MLH1 (MutL homolog 1)
    |
    TP53 mutation • MSI-H/dMMR
    27d
    Influence of Genetic Polymorphisms on the Age at Cancer Diagnosis in a Homogenous Lynch Syndrome Cohort of Individuals Carrying the MLH1:c.1528C>T South African Founder Variant. (PubMed, Biomedicines)
    The risk of a younger age at any cancer diagnosis was significantly high in LS carriers of one to two risk genotypes (Adj HR: 1.49 [CI: 1.06-2.09], corrected p = 0.030), while having one to two protective genotypes significantly reduced the risk of developing any cancer and CRC at a younger age (Adj HR: 0.52 [CI: 0.37-0.73], and Adj HR: 0.51 [CI: 0.36-0.74], both corrected p T in the MLH1 gene.
    Journal • IO biomarker
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    BCL2 (B-cell CLL/lymphoma 2) • MLH1 (MutL homolog 1) • CYP17A1 (Cytochrome P450 Family 17 Subfamily A Member 1) • TGFB1 (Transforming Growth Factor Beta 1) • PPP2R2B (Protein Phosphatase 2 Regulatory Subunit Bbeta) • CDC25C (Cell Division Cycle 25C) • GSTM1 (Glutathione S-transferase mu 1) • CYP1A1 (Cytochrome P450 Family 1 Subfamily A Member 1) • GNRP (Ras-Specific Guanine Nucleotide-Releasing Factor 1) • GSTT1 (Glutathione S-transferase theta 1) • KIF20A (Kinesin Family Member 20A)
    29d
    Suppressive cancer nonstop extension mutations increase C-terminal hydrophobicity and disrupt evolutionarily conserved amino acid patterns. (PubMed, Nat Commun)
    Analyzing the proteomes of eleven different species reveals conserved patterns of amino acid distribution in the C-terminal regions of all proteins compared to the proteomes like an enrichment of lysine and arginine and a depletion of glycine, leucine, valine and isoleucine across species and kingdoms. These evolutionary selection patterns are disrupted in the cancer-derived effective nonstop extensions.
    Journal
    |
    PTEN (Phosphatase and tensin homolog) • MLH1 (MutL homolog 1) • SMAD4 (SMAD family member 4) • B2M (Beta-2-microglobulin) • CASP8 (Caspase 8) • CDKN1B (Cyclin dependent kinase inhibitor 1B)
    |
    SMAD4 mutation
    1m
    Intraoperative rapid immunohistochemistry of microsatellite instability using non-contact alternating current electric field mixing. (PubMed, Gen Thorac Cardiovasc Surg)
    Rapid MMR-IHC could potentially serve as a clinical tool for intraoperative determination of tumor MSI/dMMR status. AC-mixing technology will contribute to improving pathological diagnostic capability through the development of an original and innovative rapid IHC.
    Journal • Microsatellite instability • MSi-H Biomarker • IO biomarker
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    |
    MSI-H/dMMR
    1m
    From colon wall to tumor niche: Unraveling the microbiome's role in colorectal cancer progression. (PubMed, PLoS One)
    Metabolic pathway analysis linked seven metabolic pathways to the microbiome. Collectively, these findings highlight significant gut microbiome alterations in CRC and strongly suggest that long-term dysbiosis profoundly impacts CRC progression.
    Journal
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    MLH1 (MutL homolog 1)
    1m
    Anticipation in families with MLH1-associated Lynch syndrome. (PubMed, Cancer)
    The current results demonstrated evidence in support of anticipation in families with MLH1-associated LS across all statistical models. Mutational effects on Mlh1 activity influenced the hazard for CRC/EC. Screening based on the youngest age of cancer diagnosis in MLH1-LS families is recommended.
    Journal
    |
    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • EPCAM (Epithelial cell adhesion molecule)
    |
    MLH1 mutation
    1m
    Cohort Study of Pancreatic Cancer Risk (clinicaltrials.gov)
    P=N/A, N=419, Active, not recruiting, Mayo Clinic | N=2000 --> 419
    Enrollment change
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • APC (APC Regulator Of WNT Signaling Pathway) • EPCAM (Epithelial cell adhesion molecule)
    |
    TP53 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • APC mutation • MSH2 mutation • PMS2 mutation
    1m
    Immunohistochemistry staining for DNA mismatch repair proteins in endoscopic biopsies and the corresponding surgical specimen in colorectal cancer. (PubMed, Rev Esp Enferm Dig)
    The correlation with results from the surgical specimen was notably high and discrepancies were primarily as a result of intratumoral heterogeneity within the same sample. The features of MMR protein loss in endoscopic biopsies can provide clinicians with valuable information for specific therapeutic approaches and genetic counseling.
    Journal • Mismatch repair • Biopsy
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    1m
    Association of glutaminase expression with immune-suppressive tumor microenvironment, clinicopathologic features, and clinical outcomes in endometrial cancer. (PubMed, Int J Gynecol Cancer)
    Our findings indicate that increased glutaminase expression is associated with an immune-suppressive tumor microenvironment, poor clinicopathologic features, and worse long-term outcomes in patients with endometrial cancer.
    Clinical data • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CD68 (CD68 Molecule) • FOXP3 (Forkhead Box P3) • GLS1 (Glutaminase)
    |
    MYC expression
    1m
    Germline DNA Damage Repair Gene Alterations in Patients with Metachronous Breast and Colorectal Cancer. (PubMed, Int J Mol Sci)
    A significant fraction of BC/CRC patients with a family history of these tumors harbored deleterious germline variants in DNA repair genes. Our findings can lead to strategies to improve the diagnosis, genetic counseling, and treatment of patients and their relatives.
    Journal
    |
    MLH1 (MutL homolog 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • MUTYH (MutY homolog) • MAD1L1 (Mitotic Arrest Deficient 1 Like 1) • NOS3 (Nitric oxide synthase 3) • LAMA1 (Laminin Subunit Alpha 1) • PABPC1 (Poly(A) Binding Protein Cytoplasmic 1)
    1m
    Long-read sequencing of an advanced cancer cohort resolves rearrangements, unravels haplotypes, and reveals methylation landscapes. (PubMed, Cell Genom)
    Promoter methylation in BRCA1 and RAD51C is a likely driver behind homologous recombination deficiency where no coding driver mutation was found. This dataset demonstrates applications for long-read sequencing in precision medicine and is available as a resource for developing analytical approaches using this technology.
    Journal • BRCA Biomarker • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MLH1 (MutL homolog 1) • RAD51C (RAD51 paralog C)
    |
    HRD
    1m
    Durvalumab for MSI-H or POLE Mutated Metastatic Colorectal Cancer (clinicaltrials.gov)
    P2, N=33, Completed, Asan Medical Center | Active, not recruiting --> Completed
    Trial completion • Mismatch repair • Tumor mutational burden • Metastases
    |
    POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    MSI-H/dMMR • POLE mutation
    |
    Imfinzi (durvalumab) • oxaliplatin • irinotecan
    1m
    MLH1 Gene Expression in Peripheral Blood in Colon Cancer Patients and Their Association with Colon Cancer. (PubMed, J Vis Exp)
    The results showed that the ratio of MLH1 gene expression in patients decreased compared to that in healthy individuals, and the decrease in gene expression at different stages of the disease was significant. The results of this study showed that the reduction of MLH1 gene expression has an effective role in the development of CRC.
    Journal
    |
    MLH1 (MutL homolog 1)
    1m
    Management of HER2-positive and microsatellite instability-high advanced gastric cancer: a case report. (PubMed, Int Cancer Conf J)
    After three cycles of S-1, oxaliplatin, and trastuzumab, the primary tumor and metastases shrank markedly...He has been recurrence-free for seven months postoperatively. The present case demonstrated the efficacy of trastuzumab-containing chemotherapy followed by conversion surgery in a patient with HER2-positive, MSI-H, advanced gastric cancer.
    Journal • Microsatellite instability • MSi-H Biomarker • IO biomarker • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1)
    |
    HER-2 positive • MSI-H/dMMR
    |
    Herceptin (trastuzumab) • oxaliplatin • Teysuno (gimeracil/oteracil/tegafur)
    1m
    MELATONIN ENHANCES TEMOZOLOMIDE-INDUCED APOPTOSIS IN GLIOBLASTOMA AND NEUROBLASTOMA CELLS. (PubMed, Exp Oncol)
    Our findings indicate that the combination of MEL with a low dose of TMZ may serve as an upstream inducer of apoptosis. This suggests the potential development of a novel selective therapeutic strategy as an alternative to TMZ for the treatment of both glioblastoma and neuroblastoma.
    Journal • IO biomarker
    |
    TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • MLH1 (MutL homolog 1) • PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma) • CASP3 (Caspase 3) • ANXA5 (Annexin A5) • SOD2 (Superoxide Dismutase 2)
    |
    BCL2 expression • TP53 expression • BAX expression
    |
    paclitaxel • temozolomide
    1m
    Association between microsatellite instability status, clinicopathological features and mitochondrial DNA amplification in patients with colorectal cancer. (PubMed, Oncol Lett)
    Furthermore, the number of mitochondrial DNA was significantly amplified in the MSI-H group. In conclusion, the present study demonstrated that the combined detection of PD-L1 and MSI in patients with CRC can provide more accurate and effective guidance for personalized treatment.
    Journal • Microsatellite instability • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • PD-1 (Programmed cell death 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
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    PD-L1 expression • BRAF V600E • MSI-H/dMMR • BRAF V600
    1m
    The molecular genetics of adrenal cushing. (PubMed, Hormones (Athens))
    Syndromic PBMAH may be due to germline pathogenic variants in MEN1, APC, or FH, causing type 1 multiple endocrine neoplasia, familial adenomatous polyposis, or hereditary leiomyomatosis-kidney cancer syndrome, respectively. PRKAR1A germline pathogenic variants are the main alteration causing PPNAD (isolated or part of Carney complex).
    Review • Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • NF1 (Neurofibromin 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • IGF2 (Insulin-like growth factor 2) • GNAS (GNAS Complex Locus) • PRKACA (Protein Kinase CAMP-Activated Catalytic Subunit Alpha) • PRKAR1A (Protein Kinase CAMP-Dependent Type I Regulatory Subunit Alpha) • CDKN1C (Cyclin Dependent Kinase Inhibitor 1C) • PRKACB (Protein Kinase CAMP-Activated Catalytic Subunit Beta) • ZNRF3 (Zinc And Ring Finger 3)
    1m
    Host repair polymorphisms and H. pylori genes in gastric disease outcomes: Who are the guardian and villains? (PubMed, Gene)
    The interaction between H. pylori genes and the host showed that the H. pylori cagE gene was the most important virulence factor associated with a worse clinical outcome, even overlapping with the XRCC1 polymorphism, where the MLH1 polymorphism response varied according to vacA alleles. Our results show the relevance of XRCC1 G > A for genome integrity, sex influence, and interaction between H. pylori virulence factors and XRCC1 and MLH1 genotypes for gastric lesion outcomes in Brazilian populations.
    Journal
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    MLH1 (MutL homolog 1) • XRCC1 (X-Ray Repair Cross Complementing 1) • XRCC3 (X-Ray Repair Cross Complementing 3)