Since new diagnostic methods such as methylome-based classification of brain tumors are more and more frequently performed, we aimed at comparing the suitability of calculating the MGMT promoter methylation status in a quantitative manner from the methylome profiling as compared to the classic gold standard assessment by PCR.
Disulfiram has also been shown to inhibit the proteasomes, DNA topoisomerases, DNA methyltransferase, glutathione S-transferase P1, and O6- methylguanine DNA methyltransferase, a DNA repair protein highly expressed in brain tumors.
Statistical multiscale mapping of IDH1, MGMT, and microvascular proliferation in human brain tumors from multiparametric MR and spatially-registered core biopsy.
O<sup>6</sup> -methylguanine DNA methyltransferase (MGMT) promoter methylation is a predictive biomarker for benefit from alkylating chemotherapy, specifically temozolomide (TMZ), in glioblastoma, the most common malignant intrinsic brain tumor.
Studies in brain tumours conclude that MGMT promoter methylation is considered a strong predictive factor for a favourable outcome for treatment with temozolomide, e.g. alkylating agent.
Surveillance, Epidemiology, and End Results (SEER) registries currently collect data on specific required factors related to brain tumors as defined by the American Joint Commission on Cancer, including World Health Organization (WHO) grade, MGMT methylation and 1p/19q codeletion status.
Analysis of MGMT promoter methylation status on intraoperative fresh tissue section from frameless neuronavigation needle biopsy of 25 patients with brain tumor.
Recently, aberrant methylation of MLH1, MGMT and MSI were shown to be associated with mutations in genes such as BRAF, RAS and IDH1 in colon and brain tumours.
The objective of this study was to retrospectively investigate MGMT promoter hypermethylation status for a series of 350 human brain tumors, including 275 gliomas of different malignancy grade, 21 glioblastoma multiforme (GBM) cell lines, and 75 non-glial tumors.
A hypermethylated phenotype is a better predictor of survival than MGMT methylation in anaplastic oligodendroglial brain tumors: a report from EORTC study 26951.
MGMT activity, promoter methylation and immunohistochemistry of pretreatment and recurrent malignant gliomas: a comparative study on astrocytoma and glioblastoma.
In this pilot study, we utilized a retroviral vector expressing methylguanine DNA methyltransferase (MGMT) to transduce hematopoietic progenitors, which were subsequently used in the setting of alkylator therapy (procarbazine, CCNU, vincristine (PCV)) for poor prognosis brain tumors.
A substantial percentage of brain tumors overexpressed biomarkers associated with drug resistance, including MGMT (67%), GSTP1 (49%), and mutant p53 (41%).
The O6-methylguanine-DNA methyltransferase protein (MGMT) reverses alkylation at the O6 position of guanine and we have reported the role of MGMT in the response of brain tumors to alkylating agents.
By removing alkyl groups from the O6-position in guanine, MGMT can prevent G:C to A:T transition mutations, a type of variation frequently involving TP53 mutations in brain tumors.
We found a significantly increased frequency of G:C to A:T mutations of the p53 gene in brain tumors having a methylated MGMT promoter compared with those having an unmethylated MGMT promoter (P < 0.05), and all the non-CpG dinucleotide G:C to A:T mutations of p53 were in samples with a methylated MGMT promoter.
We found a significantly increased frequency of G:C to A:T mutations of the p53 gene in brain tumors having a methylated MGMT promoter compared with those having an unmethylated MGMT promoter (P < 0.05), and all the non-CpG dinucleotide G:C to A:T mutations of p53 were in samples with a methylated MGMT promoter.
The data indicate that knowledge of the expression levels of MGMT and mdr1 may be particularly useful for a more rational selection of drugs which are not influenced by these resistance genes and which have improved efficacy against human brain tumors.
While the mechanism of MGMT repair has been considered to be important in the drug resistance of human brain tumors to ACNU, our present results demonstrate that beta-pol may also play an important role in the acquisition of tumor cell resistance to ACNU in human gliomas.