Quantitative analysis of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation in patients with low-grade gliomas

Sep 22, 2010Journal of neuro-oncology

Measuring MGMT Gene Control Region Methylation in Patients with Low-Grade Brain Tumors

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Abstract

MGMT promoter methylation levels ranged from 12 to 100% in 22 patients with low-grade gliomas treated with temozolomide.

Higher levels of MGMT promoter methylation are associated with better volumetric responses to chemotherapy.
The median progression-free survival for patients was 32 months.
Combined loss of heterozygosity (LOH) on chromosomes 1p and 19q was identified in 14 patients.
LOH 1p and/or 19q is correlated with a longer time to progression, but not with the radiological response to temozolomide.
Twenty patients had detectable MGMT promoter methylation, indicating its potential role as a predictive factor for treatment response.

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Methylation of the MGMT promoter is supposed to be a predictive and prognostic factor in glioblastoma. Whether MGMT promoter methylation correlates with tumor response to temozolomide in low-grade gliomas is less clear. Therefore, we analyzed MGMT promoter methylation by a quantitative methylation-specific PCR in 22 patients with histologically verified low-grade gliomas (WHO grade II) who were treated with temozolomide (TMZ) for tumor progression. Objective tumor response, toxicity, and LOH of microsatellite markers on chromosomes 1p and 19q were analyzed. Histological classification revealed ten oligodendrogliomas, seven oligoastrocytomas, and five astrocytomas. All patients were treated with TMZ 200 mg/m2 on days 1-5 in a 4 week cycle. The median progression-free survival was 32 months. Combined LOH 1p and 19q was found in 14 patients; one patient had LOH 1p alone and one patient LOH 19q alone. The LOH status could not be determined in two patients and was normal in the remaining four. LOH 1p and/or 19q correlated with longer time to progression but not with radiological response to TMZ. MGMT promoter methylation was detectable in 20 patients by conventional PCR and quantitative analysis revealed the methylation status was between 12 and 100%. The volumetric response to chemotherapy analyzed by MRI and time to progression correlated with the level of MGMT promoter methylation. Therefore, our retrospective case series suggests that quantitative methylation-specific PCR of the MGMT promoter predicts radiological response to chemotherapy with TMZ in WHO grade II gliomas.

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Quantitative analysis of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation in patients with low-grade gliomas

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