MGMT Promoter Methylation Status Predicts Survival in Pediatric Glioblastoma

Abstract

Pediatric glioblastoma (pGBM) represents 15% of pediatric brain tumors with a 3‐year survival rate of < 20%. Effective DNA repair is an important cellular mechanism for resistance to chemotherapy and radiation. The role of this mechanism in pGBM remains poorly understood. We evaluated the expression pattern of proteins (by immunohistochemistry) involved in the repair of DNA damage induced by alkylating agents, as well as, mismatch and base excision repairs including hMLH1, hMSH2 and PARP in fifteen pGBMs. MGMT promoter methylation was analyzed using methylation specific PCR and pyrosequencing. The relationship between DNA repair pathway alteration and survival was analyzed. MGMT promoter methylation was detected in 33% of tumors. Loss of hMLH1 and hMSH2 protein expression was seen in 47% and 53% of tumors, respectively. PARP expression was seen in 100% of pGBMs. hMLH1, hMSH2 and PARP expressions did not correlate with either event free survival or overall survival (p > 0.05). MGMT promoter methylation correlated significantly with better overall survival (p = 0.035). We conclude that MGMT promoter methylation status is a predictor of better survival in treated pGBM.