O6-MethylGuanine-DNA Methyltransferase (MGMT) Promoter Methylation Status Analysis in High-Grade Gliomas

Background: The O6-methylguanine- DNA methyltransferase (MGMT) gene is frequently silenced by promoter hypermethylation in malignant gliomas and this has been pinpointed as an epigenetic mechanism reducing MGMT expression levels. The status of MGMT promoter hypermethylation and its relevance to tumor progression in gliomas is under extensive study and previous studies have shown conflicting results on the significance of this epigenetic marker in relation to the tumor phenotype and clinical outcome. So, in our study, we assessed the role of the epigenetic marker; MGMT promoter methylation status, in high-grade glioma patients and correlated the results with the tumor phenotype and clinical outcome. Methods: The study included 40 high-grade glioma patients, assessed for MGMT promoter methylation status using methylation-specific PCR (MSP) and correlated the results with clinico-histopathological parameters and survival using established statistical methodologies. Results: MGMT Promoter methylation analysis revealed 65% of patients with methylated Promoter and 35% with unmethylated ones with no significant prognostic or pre­dictive value related to different treatment modalities (surgical, chemotherapy or radiation), recurrence rate, or overall survival. Conclusion: MGMT promoter methylation status role is not definitive in directing high-grade glioma patients’ clinical decision making. Further studies are needed for considering its role as an epigenetic marker in high-grade gliomas in Egyptian patients.