ArticlePloS one2011
Comprehensive analysis of MGMT promoter methylation: correlation with MGMT expression and clinical response in GBM.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 3 of them syntheses that pooled it.
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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
63 citing papers in PubMed, 3 syntheses or guidelines pooled it, 113 citations in OpenAlex.
- A systematic review of high impact CpG sites and regions for MGMT methylation in glioblastoma [A systematic review of MGMT methylation in GBM].BMC neurology · 2024Pooled it
- Accuracy of Radiomics in PredictingRadiology. Artificial intelligence · 2024Pooled it
- The role of cytoreductive surgery in the management of progressive glioblastoma : a systematic review and evidence-based clinical practice guideline.Journal of neuro-oncology · 2014Guideline
- Trial
- Surface-engineered dual drug-loaded tumor-targeted liposomal nanoparticles to overcome the therapeutic resistance in glioblastoma multiforme.Communications medicine · 2026Article
- Article
- Biodegradable nanofibrous scaffolds enhance standard of care for glioblastoma via localized targeted therapy.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Surface-engineered dual drug-loaded tumor-targeted liposomal nanoparticles to overcome the therapeutic resistance in glioblastoma multiforme.Research square · 2025Article
- Review
- Article
- Analysis of DNA Methylation in Gliomas: Assessment of Preanalytical Variables.Laboratory investigation; a journal of technical methods and pathology · 2024Article
- Molecular diversity in isocitrate dehydrogenase-wild-type glioblastoma.Brain communications · 2024Review
- Glioblastoma with high O6-methyl-guanine DNA methyltransferase expression are more immunologically active than tumors with lowFrontiers in immunology · 2024Article
- Metformin use is associated with longer survival in glioblastoma patients with MGMT gene silencing.Journal of neuro-oncology · 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
- Suppression of NANOG Expression Reduces Drug Resistance of Cancer Stem Cells in Glioblastoma.Genes · 2023Article
- MGMT and Whole-Genome DNA Methylation Impacts on Diagnosis, Prognosis and Therapy of Glioblastoma Multiforme.International journal of molecular sciences · 2022Review
- Prognostic and Predictive Biomarkers in Gliomas.International journal of molecular sciences · 2021Review
- Relative oxygen extraction fraction (rOEF) MR imaging reveals higher hypoxia in human epidermal growth factor receptor (EGFR) amplified compared with non-amplified gliomas.Neuroradiology · 2021Article
- The number of methylated CpG sites within the MGMT promoter region linearly correlates with outcome in glioblastoma receiving alkylating agents.Acta neuropathologica communications · 2021Article
3 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
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
O⁶-methylguanine DNA-methyltransferase (MGMT) promoter methylation has been identified as a potential prognostic marker for glioblastoma patients. The relationship between the exact site of promoter methylation and its effect on gene silencing, and the patient's subsequent response to therapy, is still being defined. The aim of this study was to comprehensively characterize cytosine-guanine (CpG) dinucleotide methylation across the entire MGMT promoter and to correlate individual CpG site methylation patterns to mRNA expression, protein expression, and progression-free survival. To best identify the specific MGMT promoter region most predictive of gene silencing and response to therapy, we determined the methylation status of all 97 CpG sites in the MGMT promoter in tumor samples from 70 GBM patients using quantitative bisulfite sequencing. We next identified the CpG site specific and regional methylation patterns most predictive of gene silencing and improved progression-free survival. Using this data, we propose a new classification scheme utilizing methylation data from across the entire promoter and show that an analysis based on this approach, which we call 3R classification, is predictive of progression-free survival (HR = 5.23, 95% CI [2.089-13.097], p<0.0001). To adapt this approach to the clinical setting, we used a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) test based on the 3R classification and show that this test is both feasible in the clinical setting and predictive of progression free survival (HR = 3.076, 95% CI [1.301-7.27], p = 0.007). We discuss the potential advantages of a test based on this promoter-wide analysis and compare it to the commonly used methylation-specific PCR test. Further prospective validation of these two methods in a large independent patient cohort will be needed to confirm the added value of promoter wide analysis of MGMT methylation in the clinical setting.
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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.