Dataset Information

Pyrosequencing Analysis of MGMT Promoter Methylation in Meningioma.

ABSTRACT:

Background

Methylation of the O⁶-methylguanine-DNA methyltransferase (MGMT) gene promoter is a well-established predictor of response to the DNA-alkylating agent temozolomide in patients with glioblastoma.

Materials and methods

Pyrosequencing analysis was used to determine the MGMT promoter methylation status in 61 meningiomas, to clarify whether it might have a predictive role.

Results

Only two tumors (3%) had a mean methylation frequency higher than the cut-off value of 10% for the four CpG sites examined.

Conclusion

The methylation of the MGMT promoter is uncommon, or occurs at a low frequency in meningiomas. There is no convincing rationale to test such tumors for their MGMT methylation status in a clinical setting.

SUBMITTER: Panagopoulos I

PROVIDER: S-EPMC6199576 | biostudies-literature | 2018 Sep-Oct

REPOSITORIES: biostudies-literature

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Publications

Pyrosequencing Analysis of <i>MGMT</i> Promoter Methylation in Meningioma.

Panagopoulos Ioannis I Gorunova Ludmila L Leske Henning H Niehusmann Pitt P Johannessen Lene E LE Staurseth Julie J Øino Nina N Meling Torstein R TR Heim Sverre S Micci Francesca F Brandal Petter P

Cancer genomics & proteomics 20180901 5

<h4>Background</h4>Methylation of the O<sup>6</sup>-methylguanine-DNA methyltransferase (MGMT) gene promoter is a well-established predictor of response to the DNA-alkylating agent temozolomide in patients with glioblastoma.<h4>Materials and methods</h4>Pyrosequencing analysis was used to determine the MGMT promoter methylation status in 61 meningiomas, to clarify whether it might have a predictive role.<h4>Results</h4>Only two tumors (3%) had a mean methylation frequency higher than the cut-off ...[more]

PMID: 30194078

Similar Datasets

Project description:O⁶-methylguanine DNA-methyltransferase (MGMT) promoter methylation has been identified as a potential prognostic marker for glioblastoma patients. The relationship between the exact site of promoter methylation and its effect on gene silencing, and the patient's subsequent response to therapy, is still being defined. The aim of this study was to comprehensively characterize cytosine-guanine (CpG) dinucleotide methylation across the entire MGMT promoter and to correlate individual CpG site methylation patterns to mRNA expression, protein expression, and progression-free survival. To best identify the specific MGMT promoter region most predictive of gene silencing and response to therapy, we determined the methylation status of all 97 CpG sites in the MGMT promoter in tumor samples from 70 GBM patients using quantitative bisulfite sequencing. We next identified the CpG site specific and regional methylation patterns most predictive of gene silencing and improved progression-free survival. Using this data, we propose a new classification scheme utilizing methylation data from across the entire promoter and show that an analysis based on this approach, which we call 3R classification, is predictive of progression-free survival (HR = 5.23, 95% CI [2.089-13.097], p<0.0001). To adapt this approach to the clinical setting, we used a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) test based on the 3R classification and show that this test is both feasible in the clinical setting and predictive of progression free survival (HR = 3.076, 95% CI [1.301-7.27], p = 0.007). We discuss the potential advantages of a test based on this promoter-wide analysis and compare it to the commonly used methylation-specific PCR test. Further prospective validation of these two methods in a large independent patient cohort will be needed to confirm the added value of promoter wide analysis of MGMT methylation in the clinical setting.