Ask about this productRelated genes to: MGMT protein
- Gene:
- MGMT NIH gene
- Name:
- O-6-methylguanine-DNA methyltransferase
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 10q26.3
- Locus Type:
- gene with protein product
- Date approved:
- 1989-10-16
- Date modifiied:
- 2016-10-05
Related products to: MGMT protein
Related articles to: MGMT protein
- Radiomic features are not independent: they occupy a dependency graph whose communities track acquisition sequence and tumour anatomy. Sparse selection discards that graph, but the size of the loss, whether it depends on the model discriminating, and whether it can be avoided are unknown. - Source: PubMed
Publication date: 2026/08/20
García-Hidalgo ClementeConsentino Hernández José AntonioCayuela Espí José VicentePagán Vicente GonzaloMula Ponce Juan FranciscoVázquez Olmos Ángel - Glioblastoma (GBM) is the most aggressive primary brain tumour in adults and is characterised by poor prognosis and frequent resistance to temozolomide (TMZ)-based chemotherapy. Increasing evidence suggests that long non-coding RNAs (lncRNAs) contribute to GBM progression, therapeutic adaptation, and chemoresistance. This study investigated the relationship between TMZ responsiveness and the expression of selected lncRNAs in GBM cell lines exhibiting distinct sensitivity profiles. Human GBM cell lines (A172, U87, and T98G) and normal human astrocytes (NHA) were exposed to TMZ for 24-72 h. Cell viability, cell cycle distribution, MGMT protein expression, and expression levels of nine selected lncRNAs were analysed using MTT assay, flow cytometry, Western blot, and quantitative RT-PCR, respectively. TMZ induced dose- and time-dependent reductions in cell viability in all analysed cell lines. A172 cells exhibited the greatest TMZ sensitivity, whereas T98G cells displayed the highest resistance. TMZ-sensitive GBM cells demonstrated pronounced G2/M cell cycle arrest, while T98G cells showed minimal cell cycle perturbation. MGMT protein expression was markedly elevated in T98G cells and decreased following exposure to higher TMZ concentrations. Distinct lncRNA expression profiles were identified among GBM cell lines. MALAT1 expression was consistently reduced, whereas NCK1-AS1 was strongly upregulated, particularly in T98G cells. TMZ exposure induced significant alterations in H19, PVT1, OIP5-AS1, and NCK1-AS1 expression, suggesting their potential involvement in adaptive resistance mechanisms. Collectively, these findings indicate that selected lncRNAs, particularly H19, MALAT1, NCK1-AS1, and PVT1, may contribute to TMZ resistance in GBM and could be promising biomarkers and therapeutic targets for precision oncology approaches. - Source: PubMed
Publication date: 2026/07/25
Hudáková ZuzanaHudák ĽubošHatoková ZuzanaRačay PeterHatok Jozef - Bevacizumab is widely used at recurrence in glioblastoma, but comparisons are complicated by multimodal treatment selection and progression assessment. We examined outcomes associated with a bevacizumab-containing first-recurrence strategy and explored the components of post-recurrence progression-free survival (prPFS). This retrospective single-center cohort included 166 patients at first recurrence: 114 received a bevacizumab-containing strategy and 52 a non-bevacizumab strategy. Of these, 163 had evaluable outcomes. Local therapy at first recurrence was recorded in 19.3% and 90.4% of the groups, respectively. Treatment strategy was fixed at first recurrence to reduce immortal-time bias. Analyses used pretreatment covariates, multiple imputation, propensity-score overlap weighting, robust variance estimation, and competing-risk methods. Complete-case adjusted models included 117 patients. Recurrence-specific performance status, corticosteroid exposure, and MGMT status were unavailable. Among 163 patients, 136 deaths and 145 prPFS events occurred. In the overlap-weighted analysis after multiple imputation, a bevacizumab-containing strategy was not associated with improved post-recurrence overall survival (OS; HR 1.40, 95% CI 0.93 to 2.10) or prPFS (HR 0.81, 95% CI 0.55 to 1.18). Competing-risk analysis showed a lower cause-specific hazard of documented second progression (HR 0.29, 95% CI 0.16 to 0.53) and a higher cause-specific hazard of death before documented progression, although its CI included the null (HR 1.65, 95% CI 0.93 to 2.93). Higher baseline neutrophil-to-lymphocyte ratio was associated with poorer OS (HR per doubling 1.49, 95% CI 1.20 to 1.85), but treatment interactions were inconsistent across parameterizations. A bevacizumab-containing first-recurrence strategy was not associated with improved post-recurrence OS or prPFS. Divergent progression and death patterns caution against interpreting progression-based endpoints as direct evidence of disease control in this observational setting. - Source: PubMed
Publication date: 2026/08/18
Yeşilbaş EnesGöksu Sema Sezgin - Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain cancer in adults, and treatment is frequently limited by tumor resistance to temozolomide (TMZ), the standard-of-care chemotherapy. This resistance is often driven by the tumor cell's enhanced capacity to repair TMZ-induced DNA damage. Cell division is normally controlled by two quality-control systems: the spindle assembly checkpoint (SAC), which ensures accurate chromosome segregation during mitosis, and the DNA damage response (DDR), which detects and repairs genomic damage. Growing evidence suggests these two systems are functionally connected, but whether this connection can be exploited pharmacologically in cancer remains unclear. Here, we redesigned a brain-penetrant chemical scaffold to develop G17, a small molecule that selectively inhibits monopolar spindle 1 (Mps1), the central kinase controlling SAC signaling. Characterization of G17 in biochemical and cellular models showed that Mps1 inhibition forces GBM cells to exit mitosis prematurely, resulting in persistent DNA damage and impaired long-term tumor cell growth. Notably, G17 remained active in TMZ-resistant glioblastoma cells that express O-methylguanine-DNA methyltransferase (MGMT), the enzyme primarily responsible for TMZ resistance, indicating that its activity does not depend on MGMT-mediated DNA repair. Together, these findings provide pharmacological evidence that disrupting SAC signaling can expose a DNA repair vulnerability in glioblastoma and identify Mps1 inhibition as a candidate strategy warranting further investigation in treatment-resistant disease. - Source: PubMed
Publication date: 2026/08/25
Rai GauravKirubakaran Sivapriya - Glioblastoma has been described as the most common and aggressive primary brain neoplasm in adults, with limited survival despite multimodal therapy. The prognostic impact of epidermal growth factor receptor (EGFR) amplification and its interaction with isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation remains unclear. This systematic review and meta-analysis examined how EGFR amplification level and molecular profile affect overall survival (OS) in glioblastoma. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a systematic review was performed for studies reporting OS stratified by EGFR amplification, MGMT methylation, or IDH mutation. Using a random-effects model, pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, and I² statistics were employed to assess heterogeneity. Nine studies including 1,766 subjects were analyzed. Low or moderate EGFR amplification showed no OS impact (HR=0.98 (95% CI: 0.88-1.09); HR=0.94 (95% CI: 0.81-1.10)), whereas high amplification predicted worse survival (HR=1.19; 95% CI: 1.14-1.24; p<0.00001). EGFR amplification with MGMT methylation correlated with poorer outcomes (HR=1.38; 95% CI: 1.33-1.44), while EGFR amplification with unmethylated MGMT showed improved survival (HR=0.68; 95% CI: 0.61-0.76). Stratification by IDH status identified EGFR-negative/IDH-mutant tumors as the most favorable group (HR=0.44; 95% CI: 0.29-0.67) and EGFR-positive/IDH-wildtype as the least favorable (HR=1.33; 95% CI: 0.89-2.00). High EGFR amplification independently predicts worse survival in glioblastoma, particularly with MGMT promoter methylation and IDH-wildtype status. Integrating EGFR, MGMT, and IDH profiles refines prognostic assessment and supports personalized therapeutic strategies. - Source: PubMed
Publication date: 2026/07/25
Fernandez Gomez Maria PFlorez Perdomo William AAguirre Vera Guillermo de JesusSaltaren Jesus FranciscoMoscote-Salazar Luis RVadivel Kr RajaMishra RakeshAgrawal AmitValerio Jose