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

Document Type : Original Article

Authors

1 Genetics Unit, Department of Histology & Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

2 Center of Excellence in Molecular & Cellular Medicine, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

3 Neurosurgery Department, Faculty of Medicine, Suez Canal University

4 Pathology Department, Faculty of Medicine, Mansoura University

Abstract

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 relation to tumor progression in gliomas is under extensive study and previous studies have shown conflicting results on the significance of this epigenetic biomarker in relation to the tumor phenotype and clinical outcome. So, in our study, we assessed the role of the epigenetic biomarker; 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 appropriate statistical methodologies. Results: MGMT promoter methylation analysis revealed 65% of patients with the methylated promoter and 35% with unmethylated ones with no significant prognostic or predictive implications 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 investigating its role as an epigenetic marker in high-grade gliomas in Egyptian patients.

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