MGMT promoter methylation is a predictive biomarker for benefit from alkylating agent chemotherapy in patients with IDH1-wild-type, but not IDH1-mutant, malignant gliomas of World Health Organization grades III/IV.
Aberrant methylation of the MGMT (O6-methylguanine-DNA methyltransferase) DNA-repair gene is a predictive marker for the response to chemotherapy with alkylating agents (e.g., temozolomide) in malignant gliomas.
According to pathological examination, the tumor was a high-grade glioma that was positive for methylated O-6-methylguanine-DNA methyltransferase promoter.
Currently, the most efficacious treatment for malignant gliomas is temozolomide; however, gliomas expressing the DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) are resistant to this drug.
Different molecular biomarkers were identified by genetic studies and some of these are used in neuro-oncology for the evaluation of glioma patients, in particular combined deletions of the chromosome arms 1p and 19q in oligodendroglial tumors, methylation status of the O-6 methylguanine- DNA methyltransferase gene promoter and alterations in the epidermal growth factor receptor pathway in adult malignant gliomas, isocitrate dehydrogenase 1 (IDH1) and IDH2 gene mutations in diffuse gliomas, as well as BRAF status in pilocytic astrocytomas.
Enhanced anti-tumor effect of zoledronic acid combined with temozolomide against human malignant glioma cell expressing O6-methylguanine DNA methyltransferase.
Human malignant gliomas (glioblastomas and anaplastic astrocytomas) are the most frequent brain tumors and are associated with a variety of genetic alterations including retinoblastoma (RB) and p53 gene mutations, loss of interferon alpha and beta (IFNA, IFNB) genes and lack of O6-methylguanine-DNA methyltransferase (MGMT) expression.
Immediately after the operation, mRNA expression for drug-resistance genes was investigated in frozen samples of malignant gliomas from 55 patients (30 glioblastoma multiformes, 20 anaplastic astrocytomas and 5 anaplastic oligodendroglial tumors) by real-time quantitative RT-PCR with specific primers for MGMT.
Logistic regression analysis showed that Leu84Phe of MGMT gene and pathological grade were independent risk factors for the increase of TMZ resistance in patients with malignant gliomas.
LOH of 1p in the heterogeneous population of malignant gliomas may be one of the important factors besides MGMT methylation that predict better outcome in patients treated with TMZ.
Our findings indicate that, in pHGG, (a) MGMT promoter methylation is less frequent than in adult malignant gliomas, (b) there is a high correlation between MGMT MSP and MGMT IHC, and (c) as in adults, MGMT status is associated with prognosis, although this observation has to be statistically validated on larger series of patients.
Our study identified clinicopathological factors related to postoperative seizure in HGGs and found two predictive biomarkers of postoperative seizure: MGMT and EGFR.
Prognostic significance of O6-methylguanine-DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression in anaplastic gliomas.
Recently published results of trials on elderly patients with malignant gliomas have revived the call for routine MGMT testing for clinical decision making.