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Open Access 01-12-2012 | Research

MGMT promoter methylation in gliomas-assessment by pyrosequencing and quantitative methylation-specific PCR

Authors: Annette Bentsen Håvik, Petter Brandal, Hilde Honne, Hanne-Sofie Spenning Dahlback, David Scheie, Merete Hektoen, Torstein Ragnar Meling, Eirik Helseth, Sverre Heim, Ragnhild A Lothe, Guro Elisabeth Lind

Published in: Journal of Translational Medicine | Issue 1/2012

Abstract

Background

Methylation of the O⁶-methylguanine-DNA methyltransferase (MGMT) gene promoter is a favorable prognostic factor in glioblastoma patients. However, reported methylation frequencies vary significantly partly due to lack of consensus in the choice of analytical method.

Method

We examined 35 low- and 99 high-grade gliomas using quantitative methylation specific PCR (qMSP) and pyrosequencing. Gene expression level of MGMT was analyzed by RT-PCR.

Results

When examined by qMSP, 26% of low-grade and 37% of high-grade gliomas were found to be methylated, whereas 97% of low-grade and 55% of high-grade gliomas were found methylated by pyrosequencing. The average MGMT gene expression level was significantly lower in the group of patients with a methylated promoter independent of method used for methylation detection. Primary glioblastoma patients with a methylated MGMT promoter (as evaluated by both methylation detection methods) had approximately 5 months longer median survival compared to patients with an unmethylated promoter (log-rank test; pyrosequencing P = .02, qMSP P = .06). One third of the analyzed samples had conflicting methylation results when comparing the data from the qMSP and pyrosequencing. The overall survival analysis shows that these patients have an intermediate prognosis between the groups with concordant MGMT promoter methylation results when comparing the two methods.

Conclusion

In our opinion, MGMT promoter methylation analysis gives sufficient prognostic information to merit its inclusion in the standard management of patients with high-grade gliomas, and in this study pyrosequencing came across as the better analytical method.

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Title: MGMT promoter methylation in gliomas-assessment by pyrosequencing and quantitative methylation-specific PCR
Authors: Annette Bentsen Håvik
Petter Brandal
Hilde Honne
Hanne-Sofie Spenning Dahlback
David Scheie
Merete Hektoen
Torstein Ragnar Meling
Eirik Helseth
Sverre Heim
Ragnhild A Lothe
Guro Elisabeth Lind
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Journal of Translational Medicine / Issue 1/2012
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/1479-5876-10-36

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