The CpG methylation status of the MGMT promoter strongly correlates with clinical outcome and, therefore, is used as prognostic marker during glioblastoma therapy.
Histological examination confirmed a wild-type (WT) IDH1/2, MGMT (DNA repair enzyme O6-methylguanine-DNA methyltransferase) methylated glioblastoma with a proliferative index focally as high as 20%.
In addition to its benefits for molecular subgrouping and copy number analysis of brain tumors, DNA-methylation based classification is a highly reliable tool for the assessment of MGMT promoter methylation status in glioblastoma patients.
Combined Therapy Sensitivity Index Based on a 13-Gene Signature Predicts Prognosis for IDH Wild-type and MGMT Promoter Unmethylated Glioblastoma Patients.
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.
Epigallocatechin Gallate Preferentially Inhibits O<sup>6</sup>-Methylguanine DNA-Methyltransferase Expression in Glioblastoma Cells Rather than in Nontumor Glial Cells.
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).
Clinical data (age, sex, extent of surgical resection), O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and pre-operative T2WI of 113 pathologically confirmed glioblastoma patients (from our institution, n = 61; from the Cancer Imaging Archive, n = 52) were retrospectively reviewed.
Although the two classical molecular markers of glioblastoma including isocitrate dehydrogenase 1 or 2 (IDH1/2) mutation and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation are associated with overall survival rate of glioblastoma patients, they are not specific to the survival outliers.
We discovered that RARRES1 is highly expressed in patients with mesenchymal subtype, unmethylated MGMT, IDH1 wild type, and non-G-CIMP, all of which are molecular characteristics of malignant GBM.
TMZ-naïve hypermutated tumors were marked by absence of IDH1 somatic mutation and MGMT promoter (pMGMT) methylation, two genomic traits that were significantly associated with the TMZ-induced hypermutagenic event in glioblastoma, and harbored inherited alterations in the mismatch repair (MMR) machinery.
We have assessed MGMT methylation status in blood and tissue samples from unresected glioblastoma patients who had been included in the randomized GENOM-009 trial.
We showed that ionizing radiation and temozolomide reduced the viability of cancer stem cells from GBM patients, as well as modified MGMT gene and miRNA-181d expression in cancer stem cells, suggesting that miRNA-181d interferes in the glioblastoma cancer stem cell response to treatment with temozolomide and ionizing radiation.
Patients with glioblastoma without O6-methylguanine-DNA methyltransferase (MGMT) promoter hypermethylation are unlikely to benefit from alkylating chemotherapy with temozolomide (TMZ).
Surprisingly, integrative analyses demonstrated that O6-methylguanine-DNA methyltransferase methylation and isocitrate dehydrogenase mutation status were equally distributed among glioblastoma metabolic profiles.
LC-MS/MS plasma stability assays were conducted in mice to further explore the stability profile of TMZ@Calix <i>in vivo</i> The therapeutic efficacy of TMZ@Calix was compared with that of unbound TMZ in GBM cell lines and patient-derived primary cells with known O6-methylguanine-DNA methyltransferase (<i>MGMT</i>) expression status and <i>in vivo</i> in an intracranial U87 xenograft mouse model.