Intratumoral homogeneity of MGMT promoter hypermethylation as demonstrated in serial stereotactic specimens from anaplastic astrocytomas and glioblastomas.
These include the importance of O6-methylguanine-DNA-methyltransferase (MGMT) in glioblastoma sensitivity to the DNA alkylating chemotherapy temozolomide.
Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications.
MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients.
Of note, not all patients with glioblastoma having MGMT promoter methylation respond to alkylating agents, and even those who respond will inevitably experience relapse.
Some of the most promising biomarkers to date include loss of chromosomes 1p/19q in oligodendrogliomas and expression of O-6-methylguanine-DNA methyltransferase (MGMT) or epidermal growth factor receptor (EGFR) status in glioblastomas.
MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients.
Epigenetic silencing of the DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) by promoter methylation predicts successful alkylating agent therapy, such as with temozolomide, in glioblastoma patients.
In this retrospective study, glioblastomas with low MGMT expression receiving surgical resection, radiotherapy and temozolomide capsule chemotherapy were divided into high and low mutant p53 expression groups.
The O(6)-methylguanine DNA methyltransferase (MGMT) gene encodes a DNA repair enzyme whose activity is a major mechanism of resistance to alkylating drugs in glioblastoma treatment.
This review focuses on 3 predictive molecular markers that are either in clinical use or are contemplated for use in the evaluation of malignant gliomas: assessment of 1p/19q loss in oligodendroglial tumors, examination of O6-methylguanine DNA methyltransferase promoter methylation status in glioblastomas, and molecular dissection of the epidermal growth factor receptor-phosphatidylinositol 3-kinase pathway in glioblastomas.
In fact, first steps have been undertaken in supplementing classical histopathological diagnosis by the use of molecular tests, such as MGMT promoter hypermethylation in glioblastomas or detection of losses of chromosome arms 1p and 19q in oligodendroglial tumors.
The clinical significance of other glioblastoma-associated molecular aberrations and their relationship to MGMT promoter hypermethylation is still poorly understood.
These results suggested that epigenetic inactivation of MGMT plays an important role in the survival of glioblastoma patients and this inactivated gene involved in p53 mutation.