Quantitative Mgmt Methylation Analysis By Pyrosequencing Reveals A Strong Correlation Between 1p/19q Co-Deletion And High Level Methylation In High Grade Gliomas

INTRODUCTION: Pyrosequencing is a method that allows MGMT methylation to be measured in a quantitative manner. MGMT methylation, along with 1p/19q co-deletion and IDH1 mutation, is an important biomarker in high grade gliomas. MGMT methylation indicates an improved response to temozolomide chemotherapy; patients with 1p/19q co-deleted anaplastic oligodendrogliomas benefit from the addition of chemotherapy to radiotherapy. Aim: To compare the average MGMT promoter methylation level of high grade gliomas and correlate it with other clinical parameters and markers including IDH1&2 mutation and 1p/19q co-deletion. METHOD: For 171 high grade gliomas MGMT methylation analysis was performed by pyrosequencing, mutations to IDH1 and IDH2 genes were also detected by pyrosequencing, or immunohistochemistry (n = 166). Screening for 1p/19q deletion was by fluorescence in situ hybridisation (n = 46). Statistical analysis was performed using R-Stats v2.15.2. RESULTS: The results show that higher methylation was correlated with lower grade and mutation to either IDH1 or IDH2 (27.0% vs. 16.6% p = 0.008; and 27.5 vs. 16.1 p = 0.002 respectively). Interestingly 1p/19q co-deletion versus non co-deletion was associated with a particularly high level of methylation (42.2% vs. 17.7% p = 0.001). No significant differences were seen for age or gender. CONCLUSION: The results offer a potential explanation for the improved prognosis seen in glioma patients with 1p/19q co-deletion and when combined with IDH mutation status may provide an extra control to confirm true 1p/19q co-deletion.