The RT-MSP assay that we developed in-house is a robust clinical detection method for the heterogeneous process of MGMT promoter methylation in glioblastoma.
Human brain tumors that were highly resistant to ACNU, such as glioblastoma Gbl1 and metastatic brain tumor Col1 with SD10 values (microM) of above 100, expressed markedly increased amounts of 0.95 kb MGMT mRNA.
Combined Therapy Sensitivity Index Based on a 13-Gene Signature Predicts Prognosis for IDH Wild-type and MGMT Promoter Unmethylated Glioblastoma Patients.
Consistent with this reasoning, we found that the MGMT-expressing glioblastoma cell lines exhibiting an unmethylated MGMT promoter that were pretreated with decitabine became significantly more sensitive to temozolomide.
MGMT is one of the important markers in glioblastomas as it not only predicts response to therapy but may also be used as an independent prognostic marker.
Interestingly, inhibitors of DNA methylation and histone deacetylation failed to increase MGMT protein levels in the transformed astrocyte cells as well as cultured glioblastoma cell lines, whereas the treatment partially restored mRNA levels.
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.
Temozolomide (TMZ), as the first-line chemotherapy agent used in patients with glioblastoma, has demonstrated different effects in patients due to the expression of O6-methylguanine-DNA methyltransferase (MGMT) which is able to repair the DNA lesions induced by TMZ.
While the importance of MGMT methylation is well established, we demonstrate that the combination of MGMT(methylated)/IDH1(+ve) is associated with considerably longer OS and PFS in this series of chemoradiotherapy-treated glioblastoma tumours.
There is no consensus recommendation regarding the best available treatment for patients over age 70 with glioblastoma; however, multiple studies have shown molecular characterization of glioblastoma in this group-particularly MGMT promoter methylation status-to be valuable in treatment decision making.
The pathological diagnosis was glioblastoma (GBM) with unmethylated O-6-methylguanine-DNA methyltransferase promoter and wild isocitrate dehydrogenase 1 gene.
This new NRG-GBM-RPA model improves outcome stratification over both the current RTOG RPA model and MGMT promoter methylation, respectively, for patients with GBM treated with radiation and temozolomide and was biologically validated in an independent data set.
Epigallocatechin Gallate Preferentially Inhibits O<sup>6</sup>-Methylguanine DNA-Methyltransferase Expression in Glioblastoma Cells Rather than in Nontumor Glial Cells.
Detecting the correlations between methylation and expression of MGMT and PTEN genes and GBM cancer stem cells (CSCs) markers after co-cultures with a mononuclear cell cocktail are also aims for this study.
Promoter methylation analysis of O6-methylguanine-DNA methyltransferase in glioblastoma: detection by locked nucleic acid based quantitative PCR using an imprinted gene (SNURF) as a reference.
Overexpression of macrophage migration inhibitory factor (MIF) was identified in human GBM specimens that were MGMT methylated but showed poor survival.
The standard deviation (SD) of rCBV was significantly higher in glioblastoma (GBM) with methylated O6-methylguanine DNA methyltransferase (MGMT; 1.99 ± 0.73; p = 0.001) than in those with unmethylated MGMT (1.20 ± 0.45).