ArticleNeuro-oncology advances
Defining the recommended gray zone in O6-methylguanine-DNA methyltransferase promoter methylation pyrosequencing reporting: A robust, translatable method to implement new EANO guidelines.
Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Clinical Impact of MGMT Promoter Methylation in IDH-Mutant Gliomas: Influence of Threshold Selection and Clinical Confounding.Annals of clinical and translational neurology · 2026Article
- MGMT promoter methylation across glioma subtypes: biological relevance, treatment response, and survival outcomes.Molecular biology reports · 2026Review
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) may cause resistance of tumor cells to alkylating agents and is a predictive biomarker in high-grade gliomas treated with temozolomide. Recent European Association of Neuro-Oncology (EANO) guidelines recommend internal validation of MGMT methylation cutoffs and reporting of gray zone values. This study aimed to develop a method to derive a gray zone from pyrosequencing MGMT methylation data. Methods: We developed a method to find the optimal gray zone using pyrosequencing MGMT methylation values (CpG sites 72-83) from 308 glioblastoma cases with overall survival data. Each integer below the methylated threshold defined a new possible gray zone and categorization which was used as a variable in a multivariate Cox proportional hazards regression model. The optimal gray zone was selected as the option that had a statistically different survival function from the methylated and unmethylated groups, with the largest log-likelihood ratio test statistic. We applied the method to a validation cohort of 115 glioblastoma cases. Results: Our method successfully identified a gray zone in our development cohort. The following categorization gave 3 distinct survival functions: methylated ≥12% ( Conclusions: We have developed a translatable method to identify the optimal MGMT gray zone from pyrosequencing data in line with recent EANO guidelines, to enhance clinical decision-making.
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