<i>O</i>(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation is a high predictive factor for therapy results of temozolomide in patients with glioma.
MGMT (O(6)-methylguanine-DNA methyltransferase) controls DNA repair pathways, and its epigenetic silencing is used for predicting the response to the alkylating drug temozolomide in patients with glioma.
Then, we also analyzed the impact of TERT promoter mutations, PTEN deletion, EGFR amplification and MGMT promoter methylation in diagnosis, prognosis and response to therapy in glioma molecular subgroup.
Currently, three molecular markers, related to better outcome, are particularly useful and complement the histological classification: the 1p/19q codeletion strongly predicts prolonged response to treatment and prolonged survival in oligodendroglial tumors; the O(6)-methylguanine-DNA methyltransferase promoter methylation, which is hypothesized to render the cell more vulnerable to alkylants, is associated with a stronger benefit of concomitant chemoradiotherapy in glioblastomas; mutations of the IDH1 (more rarely IDH2) gene affects 40% of gliomas (but 100% of the 1p/19q codeleted gliomas) and is inversely correlated to grade.
The median methylation level of MGMT in glioma samples was 64.65% (IQR, 54.87%-74.37%) compared to 38.30% (IQR, 34.13%-45.45%) in healthy controls, and all revealed significant differences including P16.
This study aimed to build a radiomics signature based on <sup>18</sup>F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for noninvasive measurement of the MGMT promoter methylation status in glioma.
Finally, we determined that the sensitivity of each primary GBM cells and glioma cell lines to the lomeguatrib-TMZ combination was different and significantly associated with the structure of MGMT methylation.
This review summarizes the existing data that support the rationale for MGMT promoter methylation testing and possibly other molecular testing in clinically defined glioma subtypes.
Ninety-two percent of tumor samples were methylated for RASSF1A, 30%-57% for BLU and 47% for MGMT, suggesting promoter methylation of these genes to be a common event in glioma tumorigenesis.
Here, we demonstrated that (1) IDH1/2 mutation is closely correlated with MGMT promoter methylation and 1p/19q codeletion in LGGs, (2) LINE-1 methylation levels in primary and secondary GBMs are lower than those in LGGs and normal brain tissues, (3) LINE-1 methylation is proportional to MGMT promoter methylation in gliomas, and (4) higher LINE-1 methylation is a favorable prognostic factor in primary GBMs, even compared to MGMT promoter methylation.
The gene encoding the DNA repair enzyme O (6)-methylguanine-DNA methyltransferase (MGMT) is transcriptionally silenced by promoter methylation in several human tumors, including gliomas and systemic lymphomas.
We studied tumor purity, pTERT mutation by Sanger sequencing, MGMT methylation by pyrosequencing, IDH1 mutation status, and clinical parameters in a cohort of high-grade gliomas (<i>n</i> = 97).
There was an inverse correlation of MGMT promoter methylation frequency with tumor grade, observed in 79.4%, 70.8%, and 56.8% of grade II, grade III, and grade IV gliomas, respectively.
O6-Methylguanine-methyltransferase (MGMT) promoter methylation status in glioma stem-like cells is correlated to temozolomide sensitivity under differentiation-promoting conditions.
A previous study using the RNA microarray technique showed that decrease of MGMT mRNA stands out among the alterations in gene expression caused by the cell growth-depressing transfection of a T98G glioma cell line with liver-type glutaminase (LGA) [Szeliga et al.(2009) Glia, 57, 1014].
The basal promoter in glioma cells with minimal MGMT expression, however, which is 75% unmethylated, was much less accessible, and the basal promoter in nonexpressing cells, which is 50% unmethylated, was entirely inaccessible to restriction enzymes.
Chemoresistance to temozolomide in human glioma cell line U251 is associated with increased activity of O6-methylguanine-DNA methyltransferase and can be overcome by metronomic temozolomide regimen.