EG-02 * CORRELATION OF MGMT PROMOTER METHYLATION STATUS ANALYSIS USING 6 MS-MLPA PROBES AND CLINICAL RESPONSE OF TEMOZOLOMIDE IN GLIOBLASTOMA PATIENTS

Abstract

INTRODUCTION: For patients diagnosed with Glioblastoma Multiforme (GBM) O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is an important predictive factor for treatment with temozolomide (TMZ). MGMT reverses the toxic effect of alkylating chemotherapies like TMZ, therefore absence of the MGMT protein, due to promoter hypermethylation, results in greater tumor response and prolonged survival. MGMT methylation status can be determined using Methylation Specific Multiplex Ligation-dependent Probe Amplification (MS-MLPA). Previous research has documented the predictive value of MGMT MS-MLPA probe mix ME011-A1 containing 3 MGMT probes, but no documentation is available for the current commercially available MS-MLPA probe mix ME011-B containing 6 MGMT probes. The aim of this study is to determine the predictive value of MGMT promoter methylation status for GBM patients using the ME011-B probe mix. METHODS: Patients were included if diagnosed with GBM and treated with TMZ. Retrospectively 102 patients were evaluated for MGMT promoter methylation using the MS-MLPA probe mix ME011-B. Methylation status was compared to clinical outcome to determine the predictive value of MS-MLPA promoter methylation status determined by ME011-B probes. Comparison of methylation status with clinical response was also used to determine which combination of probes provides the best prediction of the response to TMZ. RESULTS: Preliminary MS-MLPA results of 79 patients indicate that the number of patients with promoter hypermethylation in tumors ranges from 15%-67% depending on the probe using a cut-off value of >25%. However, when eliminating the lowest and highest probe and calculating the mean, 65% of the tumors show hypermethylation. CONCLUSION: MGMT promoter methylation status was determined using MS-MLPA probe mix ME011-B, results indicate that over half of the patients diagnosed with GBM might benefit from TMZ therapy. Obtaining clinical response of patients and further analysis is necessary to determine the predictive value of MGMT promoter methylation status determined by MS-MLPA ME011-B probes.