ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2019
A novel analytical model of MGMT methylation pyrosequencing offers improved predictive performance in patients with gliomas.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Pyrosequencing versus methylation-specific PCR for assessment of MGMT methylation in tumor and blood samples of glioblastoma patients.Scientific reports · 2019Trial
- Quantitative DNA melting analysis with hybridization probes (qDMA-HP) as a novel approach to assess MGMT promoter methylation in malignant glioma.Journal of neuro-oncology · 2026Article
- Beyond the Promoter: Total MGMT Gene Methylation Modulates Response to DNA-Alkylating Agents in Glioma.Molecular cancer therapeutics · 2025Article
- DNA Methylation Analysis by Bisulfite Pyrosequencing of Mouse Embryonic Fibroblasts with Reprogramming Enhanced by Thyroid Hormones.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Unveiling hierarchy and spatial distribution of OCancer science · 2024Article
- Accurate and rapid molecular subgrouping of high-grade glioma via deep learning-assisted label-free fiber-optic Raman spectroscopy.PNAS nexus · 2024Article
- Genome-wide DNA methylation analysis identifies potent CpG signature for temzolomide response in non-G-CIMP glioblastomas with unmethylated MGMT promoter: MGMT-dependent roles of GPR81.CNS neuroscience & therapeutics · 2024Article
- Identification of the E2F1-RAD51AP1 axis as a key factor in MGMT-methylated GBM TMZ resistance.Cancer biology & medicine · 2023Article
- Clinical management and survival outcomes of patients with different molecular subtypes of diffuse gliomas in China (2011-2017): a multicenter retrospective study from CGGA.Cancer biology & medicine · 2022Article
- Volumetric Analysis of Glioblastoma for Determining Which CpG Sites Should Be Tested by Pyrosequencing to Predict Temozolomide Efficacy.Biomolecules · 2022Article
- MGMT and Whole-Genome DNA Methylation Impacts on Diagnosis, Prognosis and Therapy of Glioblastoma Multiforme.International journal of molecular sciences · 2022Review
- MGMT gene promoter methylation by pyrosequencing method correlates volumetric response and neurological status in IDH wild-type glioblastomas.Journal of neuro-oncology · 2022Article
- Expression and Potential Biomarkers of Regulators for M7G RNA Modification in Gliomas.Frontiers in neurology · 2022Article
- Combining MGMT promoter pyrosequencing and protein expression to optimize prognosis stratification in glioblastoma.Cancer science · 2021Article
- Clinical validation of a novel quantitative assay for the detection of MGMT methylation in glioblastoma patients.Clinical epigenetics · 2021Article
- Predictive value of MGMT promoter methylation on the survival of TMZ treatedCancer biology & medicine · 2021Article
- A Signature of Nine lncRNA Methylated Genes Predicts Survival in Patients With Glioma.Frontiers in oncology · 2021Article
- [ALKBH5 suppresses migration and invasion of human trophoblast cells by inhibiting epithelial-mesenchymal transition].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2020Article
- Clinicopathological characteristics and survival of spinal cord astrocytomas.Cancer medicine · 2020Article
- A novel Cas9-targeted long-read assay for simultaneous detection of IDH1/2 mutations and clinically relevant MGMT methylation in fresh biopsies of diffuse glioma.Acta neuropathologica communications · 2020Article
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8 authors.
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Abstract
The methylation status of the promoter of MGMT gene is a crucial factor influencing clinical decision-making in patients with gliomas. MGMT pyrosequencing results are often dichotomized by a cut-off value based on an average of several tested CpGs. However, this method frequently results in a "gray zone", representing a dilemma for physicians. We therefore propose a novel analytical model for MGMT methylation pyrosequencing. MGMT CpG heterogeneity was investigated in 213 glioma patients in two tested cohorts: cohort A in which CpGs 75-82 were tested and cohort B in which CpGs 72-78 were tested. The predictive performances of the novel and traditional averaging models were compared in 135 patients who received temozolomide using receiver operating characteristic curves and Kaplan-Meier curves, and in patients stratified according to isocitrate dehydrogenase gene mutation status. The results were validated in an independent cohort of 65 consecutive patients with high-grade gliomas from the Chinese Glioma Genome Atlas database. Heterogeneity of MGMT promoter CpG methylation level was observed in most gliomas. The optimal cut-off value for each individual CpG varied from 4-16%. The current analysis defined MGMT promoter methylation as occurring when at least three CpGs exceeded their respective cut-off values. This novel analysis could accurately predict the prognosis of patients in the methylation "gray zone" according to the standard averaging method, and improved the area under the curves from 0.67, 0.76, and 0.67 to 0.70, 0.84, and 0.72 in cohorts A, B, and the validation cohort, respectively, demonstrating superiority of this analytical method in all three cohorts. Furthermore, the advantages of the novel analysis were retained regardless of WHO grade and isocitrate dehydrogenase gene mutation status. In conclusion, this novel analytical model offers an improved clinical predictive performance for MGMT pyrosequencing results and is suitable for clinical use in patients with gliomas.
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