ArticleThe Journal of clinical investigation2003
Inactivation of hMLH1 and hMSH2 by promoter methylation in primary non-small cell lung tumors and matched sputum samples.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 138 citations in OpenAlex.
- Acquired resistance of cancer therapies: Mechanisms and perspectives.Chinese medical journal · 2026Review
- Machine Learning-Based Pathomics Signature in Predicting MSH2 Expression and Prognosis in Gastric Cancer.Clinical and translational gastroenterology · 2026Article
- Lung cancer clustering by identification of similarities and discrepancies of DNA copy numbers using maximal information coefficient.PloS one · 2024Article
- Improving targeted small molecule drugs to overcome chemotherapy resistance.Cancer reports (Hoboken, N.J.) · 2024Review
- DNA Damage Response in Cancer Therapy and Resistance: Challenges and Opportunities.International journal of molecular sciences · 2022Review
- A Pan-Cancer Analysis on the Systematic Correlation of MutS Homolog 2 (MSH2) to a Malignant Tumor.Journal of oncology · 2022Article
- Review
- DNA Methylation Markers in Lung Cancer.Current genomics · 2021Review
- Resolving DNA Damage: Epigenetic Regulation of DNA Repair.Molecules (Basel, Switzerland) · 2020Review
- Extracellular Vesicles and Epigenetic Modifications Are Hallmarks of Melanoma Progression.International journal of molecular sciences · 2019Review
- Hypermethylation of mismatch repair gene hMSH2 associates with platinum-resistant disease in epithelial ovarian cancer.Clinical epigenetics · 2019Article
- Molecular mutation characteristics of mismatch and homologous recombination repair genes in gastrointestinal cancer.Oncology letters · 2019Article
- Article
- Epigenetic heterogeneity in cancer.Biomarker research · 2019Review
- Identification of Key Genes and Pathways in Female Lung Cancer Patients Who Never Smoked by a Bioinformatics Analysis.Journal of Cancer · 2019Article
- Aberrant methylation of mutL homolog 1 is associated with increased risk of non-small cell lung cancer.Journal of clinical laboratory analysis · 2018Article
- Epigenetic silencing of miR-493 increases the resistance to cisplatin in lung cancer by targeting tongue cancer resistance-related protein 1(TCRP1).Journal of experimental & clinical cancer research : CR · 2017Article
- Small suitability of the DLEC1, MLH1 and TUSC4 mRNA expression analysis as potential prognostic or differentiating markers for NSCLC patients in the Polish population.Journal of genetics · 2017Article
- miR-196b Is Epigenetically Silenced during the Premalignant Stage of Lung Carcinogenesis.Cancer research · 2016Article
- Expression level and methylation status of three tumor suppressor genes, DLEC1, ITGA9 and MLH1, in non-small cell lung cancer.Medical oncology (Northwood, London, England) · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We performed a genetic and epigenetic study of the hMLH1 and hMSH2 mismatch repair genes in resected primary tumors from 77 non-small cell lung cancer (NSCLC) patients. The molecular alterations examined included the loss of mRNA and protein expression as well as promoter methylation, and the allelic imbalance of the chromosomal regions that harbor the genes. We found that 78% and 26% of patients showed at least one type of molecular alteration within the hMLH1 and hMSH2 genes, respectively. Promoter methylation of the hMLH1 gene was present in 55.8% of tumors, and was significantly associated with the reduction in mRNA and protein expression (P = 0.001). A 72% concordance of aberrant methylation in sputum samples with matched resected tumors was found. In addition, a 93% consistency between the promoter methylation and the mRNA expression of the hMSH2 gene was found in 14 female NSCLC patients. However, no correlation was found between the expression of hMLH1 and hMSH2 proteins and the allelic imbalance of five microsatellite markers closely linked to the genes. Our results suggest that hMLH1 is the major altered mismatch repair gene involved in NSCLC tumorigenesis, and that promoter methylation is the predominant mechanism in hMLH1 and hMSH2 deregulation. In addition, promoter methylation of the hMLH1 gene may be identified in sputum samples to serve as a potential diagnostic marker of NSCLC.
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