• Miyuki Uno, Sueli Mieko Oba-Shinjo, Anamaria Aranha Camargo, Ricardo Pereira Moura, Paulo Henrique de Aguiar, Hector Navarro Cabrera, Marcos Begnami, Sérgio Rosemberg, Manoel Jacobsen Teixeira, and Suely Kazue Nagahashi Marie.
• Department of Neurology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil. unomiyuki@lim15.fm.usp.br
• Clinics (Sao Paulo). 2011 Jan 1; 66 (10): 1747-55.

Objectives1) To correlate the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter to its gene and protein expression levels in glioblastoma and 2) to determine the most reliable method for using MGMT to predict the response to adjuvant therapy in patients with glioblastoma.BackgroundThe MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas, and this modification has emerged as a relevant predictor of therapeutic response.MethodsFifty-one cases of glioblastoma were analyzed for MGMT promoter methylation by methylation-specific PCR and pyrosequencing, gene expression by real time polymerase chain reaction, and protein expression by immunohistochemistry.ResultsMGMT promoter methylation was found in 43.1% of glioblastoma by methylation-specific PCR and 38.8% by pyrosequencing. A low level of MGMT gene expression was correlated with positive MGMT promoter methylation (p = 0.001). However, no correlation was found between promoter methylation and MGMT protein expression (p = 0.297). The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (log rank = 0.025 by methylation-specific PCR and 0.004 by pyrosequencing), and methylation was an independent predictive factor that was associated with improved prognosis by multivariate analysis.Discussion And ConclusionMGMT promoter methylation status was a more reliable predictor of susceptibility to adjuvant therapy and prognosis of glioblastoma than were MGMT protein or gene expression levels. Methylation-specific polymerase chain reaction and pyrosequencing methods were both sensitive methods for determining MGMT promoter methylation status using DNA extracted from frozen tissue.

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