Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma
Clinics
; 66(10): 1747-1755, 2011. ilus, graf, tab
Artigo
em Inglês
| LILACS
| ID: lil-601909
Biblioteca responsável:
BR1.1
ABSTRACT
OBJECTIVES: 1) 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. 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: Fifty-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. RESULTS: MGMT promoter methylation was found in 43.1 percent of glioblastoma by methylation-specific PCR and 38.8 percent 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 CONCLUSION: MGMT 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.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
LILACS
Assunto principal:
Neoplasias Encefálicas
/
Metilases de Modificação do DNA
/
Regiões Promotoras Genéticas
/
Glioblastoma
/
Proteínas Supressoras de Tumor
/
Enzimas Reparadoras do DNA
Tipo de estudo:
Estudo prognóstico
Limite:
Adolescente
/
Adulto
/
Idoso
/
Feminino
/
Humanos
/
Masculino
Idioma:
Inglês
Revista:
Clinics
Assunto da revista:
Medicina
Ano de publicação:
2011
Tipo de documento:
Artigo
/
Documento de projeto
País de afiliação:
Brasil
Instituição/País de afiliação:
Diagnostika/BR
/
Hospital Alemão Oswaldo Cruz/BR
/
Universidade de São Paulo/BR