An experience of Methylguanine-DNA Methylation Assay (MGMT) characterization in glial tumors

Background: MGMT (O6-methylguanine DNA methyltransferase) is a DNA repair enzyme, that rescues tumor cells from damage by alkylating agents like temozolomide (TMZ). Promotor methylation of MGMT leads to epigenetic silencing and potentially increased sensitivity to TMZ. MGMT methylation (mMGMT) is an independent favorable prognostic factor, and has confounded its role as a predictive biomarker in making therapeutic decisions for glial tumors, particularly glioblastoma multiforme (GBM). Materials and Methods: This retrospective cross-sectional study was conducted for 5 years in high-grade tumors (HCG) Cancer Hospital between January 2016 and December 2020. Methylation-specific polymerase chain reaction of MGMT gene using bisulfite modification of tumor DNA was utilized to ascertain the methylation status of cases in the cohort. Results: A total of 54 glial tumors comprising 35 males and 18 females between the age group 11 years to 76 years underwent mMGMT testing. About 64.8% (35 cases) of all glial tumors demonstrated mMGMT in the cohort; GBM accounting for a majority of the cases (80.0%; 28 cases). The percentage of mMGMT cases in males and females was found to be 60.0% and 73.0% of cases, respectively. The confluent necrosis commonly seen in GBM is present in 41.0% of methylated cases and minimal in 77.3% of unmethylated cases with a significant P < 0.05. Conclusion: MMGMT is a valuable predictive biomarker and is essential in taking the therapeutic decision in newly diagnosed glial tumors. Necrosis can be used as an indicator of mMGMT status according to the present study.