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Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma
Uno, Miyuki; Oba-Shinjo, Sueli Mieko; Camargo, Anamaria Aranha; Moura, Ricardo Pereira; Aguiar, Paulo Henrique de; Cabrera, Hector Navarro; Begnami, Marcos; Rosemberg, Sérgio; Teixeira, Manoel Jacobsen; Marie, Suely Kazue Nagahashi.
  • Uno, Miyuki; Universidade de São Paulo. Faculdade de Medicina. Department of Neurology. São Paulo. BR
  • Oba-Shinjo, Sueli Mieko; Universidade de São Paulo. Faculdade de Medicina. Department of Neurology. São Paulo. BR
  • Camargo, Anamaria Aranha; Hospital Alemão Oswaldo Cruz. Ludwig Institute for Cancer Research. São Paulo. BR
  • Moura, Ricardo Pereira; Hospital Alemão Oswaldo Cruz. Ludwig Institute for Cancer Research. São Paulo. BR
  • Aguiar, Paulo Henrique de; Universidade de São Paulo. Faculdade de Medicina. Department of Neurology. São Paulo. BR
  • Cabrera, Hector Navarro; Universidade de São Paulo. Faculdade de Medicina. Department of Neurology. São Paulo. BR
  • Begnami, Marcos; Diagnostika. São Paulo. BR
  • Rosemberg, Sérgio; Universidade de São Paulo. Faculdade de Medicina. Department of Pathology. São Paulo. BR
  • Teixeira, Manoel Jacobsen; Universidade de São Paulo. Faculdade de Medicina. Department of Neurology. São Paulo. BR
  • Marie, Suely Kazue Nagahashi; Universidade de São Paulo. Faculdade de Medicina. Department of Neurology. São Paulo. BR
Clinics ; 66(10): 1747-1755, 2011. ilus, graf, tab
Article in English | LILACS | ID: lil-601909
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.
Subject(s)


Full text: Available Index: LILACS (Americas) Main subject: Brain Neoplasms / DNA Modification Methylases / Promoter Regions, Genetic / Glioblastoma / Tumor Suppressor Proteins / DNA Repair Enzymes Type of study: Prognostic study Limits: Adolescent / Adult / Aged / Female / Humans / Male Language: English Journal: Clinics Journal subject: Medicine Year: 2011 Type: Article / Project document Affiliation country: Brazil Institution/Affiliation country: Diagnostika/BR / Hospital Alemão Oswaldo Cruz/BR / Universidade de São Paulo/BR

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Full text: Available Index: LILACS (Americas) Main subject: Brain Neoplasms / DNA Modification Methylases / Promoter Regions, Genetic / Glioblastoma / Tumor Suppressor Proteins / DNA Repair Enzymes Type of study: Prognostic study Limits: Adolescent / Adult / Aged / Female / Humans / Male Language: English Journal: Clinics Journal subject: Medicine Year: 2011 Type: Article / Project document Affiliation country: Brazil Institution/Affiliation country: Diagnostika/BR / Hospital Alemão Oswaldo Cruz/BR / Universidade de São Paulo/BR