2019•Journal of Cancer TherapyOpen access

Impact of MGMT Promoter Methylation as a Prognostic Marker in Patients with High Grade Glioma: A Single-Center Observational Study

Vinu Sarathy, Srinivas Belagutty Jayappa, Bhanu Prakash Lalkota, Kiran Pura Krishnamurthy, Vishal Kulkarni, Samuel Luke Koramati, Mohammad Nasiruddin, Radheshyam Naik

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Abstract

Objectives: 1) To correlate the methylation status of the O-6-methylguanine-DNA-methyltransferase (MGMT promoter gene) and response to alkylating agent-based treatment in high-grade gliomas. Background: The MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas and this modification has emerged as a relevant predictor of therapeutic response. Methods: 20 cases of high-grade glioma were analyzed for MGMT promoter methylation by methylation-specific PCR. Response to treatment and overall survival data were recorded and data analysed. Results: MGMT promoter methylation was found in 60% of gliomas by methylation-specific PCR. The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (P = 0.035) and methylation status was an independent predictive factor that was associated with improved prognosis. Discussion and Conclusion: MGMT promoter methylation status was a more reliable predictor of response to adjuvant therapy and prognosis of high-grade gliomas. A subset of patients received irinotecan and bevacizumab in the second line setting and patients with unmethylated MGMT seemed to do better than the MGMT promoter methylated group.

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Objectives: 1) To correlate the methylation status of the O-6-methylguanine-DNA-methyltransferase (MGMT promoter gene) and response to alkylating agent-based treatment in high-grade gliomas. Background: The MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas and this modification has emerged as a relevant predictor of therapeutic response. Methods: 20 cases of high-grade glioma were analyzed for MGMT promoter methylation by methylation-specific PCR. Response to treatment and overall survival data were recorded and data analysed. Results: MGMT promoter methylation was found in 60% of gliomas by methylation-specific PCR. The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (P = 0.035) and methylation status was an independent predictive factor that was associated with improved prognosis. Discussion and Conclusion: MGMT promoter methylation status was a more reliable predictor of response to adjuvant therapy and prognosis of high-grade gliomas. A subset of patients received irinotecan and bevacizumab in the second line setting and patients with unmethylated MGMT seemed to do better than the MGMT promoter methylated group.

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Available abstract

Objectives: 1) To correlate the methylation status of the O-6-methylguanine-DNA-methyltransferase (MGMT promoter gene) and response to alkylating agent-based treatment in high-grade gliomas. Background: The MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas and this modification has emerged as a relevant predictor of therapeutic response. Methods: 20 cases of high-grade glioma were analyzed for MGMT promoter methylation by methylation-specific PCR. Response to treatment and overall survival data were recorded and data analysed. Results: MGMT promoter methylation was found in 60% of gliomas by methylation-specific PCR. The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (P = 0.035) and methylation status was an independent predictive factor that was associated with improved prognosis. Discussion and Conclusion: MGMT promoter methylation status was a more reliable predictor of response to adjuvant therapy and prognosis of high-grade gliomas. A subset of patients received irinotecan and bevacizumab in the second line setting and patients with unmethylated MGMT seemed to do better than the MGMT promoter methylated group.

Key concepts: Methylation, Glioma, Methyltransferase, Temozolomide, Irinotecan, Bevacizumab, Oncology, DNA methylation

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