ArticleOncogene2003
Silencing effect of CpG island hypermethylation and histone modifications on O6-methylguanine-DNA methyltransferase (MGMT) gene expression in human cancer.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
93 citing papers in PubMed, 182 citations in OpenAlex.
- High levels of circulating folate concentrations are associated with DNA methylation of tumor suppressor and repair genesClinical epigenetics · 2017Trial
- Phase II study of temozolomide and veliparib combination therapy for sorafenib-refractory advanced hepatocellular carcinoma.Cancer chemotherapy and pharmacology · 2015Trial
- MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC Brain Tumor Group Study 26951.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2009Trial
- TPGS-stabilized pyrimethamine micelles promote ROS-associated apoptosis in MDA-MB-231 cells and suppress tumour progression in a murine lymphoma model.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Article
- Brain Cancer: Molecular Alterations and Emerging Trends in Neuropharmacology.International journal of molecular sciences · 2026Review
- Association Between MGMT Promoter Methylation and Clinical and Lifestyle Factors in Glioblastoma: A Single-Center Study in Korea.Journal of clinical medicine · 2026Article
- Analytical validation of the Belay Vantage™ assay for evaluation of MGMT promoter methylation using enzymatically converted tumorDNA from cerebrospinal fluid.Cancer genetics · 2025Article
- Fission yeast Caprin protein is required for efficient heterochromatin establishment.PLoS genetics · 2025Article
- Genetic and epigenetic landscape of OExploration of targeted anti-tumor therapy · 2025Review
- 'The Reports of My Death Are Greatly Exaggerated'-Evaluating the Effect of Necrosis onCancers · 2024Article
- Association ofCancers · 2023Article
- MGMT methylation pattern of long-term and short-term survivors of glioblastoma reveals CpGs of the enhancer region to be of high prognostic value.Acta neuropathologica communications · 2023Article
- Expression of IL-13Rα2 and FUS in glioma: clinicopathological and prognostic correlation.BMC neurology · 2023Article
- A Promising Way to Overcome Temozolomide Resistance through Inhibition of Protein Neddylation in Glioblastoma Cell Lines.International journal of molecular sciences · 2023Article
- Comprehensive clinical assays for molecular diagnostics of gliomas: the current state and future prospects.Frontiers in molecular biosciences · 2023Review
- Current advances in temozolomide encapsulation for the enhancement of glioblastoma treatment.Theranostics · 2023Review
- ITGB3BP is a potential biomarker associated with poor prognosis of glioma.Journal of cellular and molecular medicine · 2022Article
- Separable roles for RNAi in regulation of transposable elements and viability in the fission yeast Schizosaccharomyces japonicus.PLoS genetics · 2022Article
- DNA Repair Mechanisms and Therapeutic Targets in Glioma.Current oncology reports · 2021Review
- Association between H3K36me3 modification and methylation ofToxicology research · 2020Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
O6-methylguanine-DNA methyltransferase (MGMT) repairs the cytotoxic and mutagenic O6-alkylguanine produced by alkylating agents such as chemotherapeutic agents and mutagens. Recent studies have shown that in a subset of tumors, MGMT expression is inversely linked to hypermethylation of the CpG island in the promoter region; however, how the epigenetic silencing mechanism works, as it relates to hypermethylation, was still unclear. To understand the mechanism, we examined the detailed methylation status of the whole island with bisulfite-sequencing in 19 MGMT non-expressed cancer cell lines. We found two highly methylated regions in the island. One was upstream of exon 1, including minimal promoter, and the other was downstream, including enhancer. Reporter gene assay showed that methylation of both the upstream and downstream regions suppressed luciferase activity drastically. Chromatin immunoprecipitation assay revealed that histone H3 lysine 9 was hypermethylated throughout the island in the MGMT negative line, whereas acetylation on H3 and H4 and methylation on H3 lysine 4 were at significantly high levels outside the minimal promoter in the MGMT-expressed line. Furthermore, MeCP2 preferentially bound to the CpG-methylated island in the MGMT negative line. Given these results, we propose a model for gene silencing of MGMT that is dependent on the epigenetic state in cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.