Abstract:

Aims: Glioblastomas are the most malignant gliomas in adults with the median survival of 15 months only. O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme which overcomes the alkylating chemotherapy effect resulting in chemo-resistance. Methylation at the MGMT gene promoter reduces the gene expression and enhances chemo-sensitivity in cancer treatments. Therefore, this study aimed to screen MGMT methylation status for a potential epigenetic biomarker in glioma detection and treatmentin glioma patients at Hospital Universiti Sains Malaysia. Methods: Forty-one glioma paraffin-embedded glioma tissue samples consisting of grade 2 (n=11), 3 (n=10) and 4 (n=20) were analyzed in this retrospective study. The extracted DNA was subjected to bisulfite treatment and the methylation status was determined via methylation-specific polymerase chain reaction targeting the MGMT gene promoter. Results: It was observed that 92.7% of the glioma samples showed methylated and 7.3% unmethylated MGMT promoter. All grade 2 and grade 3 gliomas showed methylation, compared to 85% of grade 4 (p=0.183). More older glioma patients (>40 years) had methylation compared to younger patients (≤40 years) (95.8% vs 88.2%) (p=0.357). More males had methylation compared to females (96% vs 87.5%) (p=0.308). Conclusions: MGMT promoter methylation was found predominant in older (>40 years) male patients with grade 2 and 3 gliomas. High percentages of gliomas, 92.7% harboring methylated MGMT promoter, indicate that it is a potential epigenetic biomarker for glioma detection.

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