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
- Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, and virtually all patients relapse on standard temozolomide (TMZ) plus radiotherapy. The molecular mechanisms that allow residual tumor cells to survive treatment, reshape the microenvironment, and seed a drug-resistant recurrence remain incompletely understood. We analyzed paired bulk RNA-seq from 13 primary-recurrent patient pairs (GSE139533), used two published primary GBM single-cell/single-nucleus samples (GSE138794/GSM4119534 and GSE174554/GSM5319503; 5244 quality-controlled cells/nuclei) solely for cellular-context mapping, and evaluated an exploratory bulk-derived gene set in TCGA-GBM. Paired testing of 18,445 genes identified one significant gene at FDR 〈 0.05 and |log2FC| 〉 0.3: IL4I1 (log2FC = 1.49, FDR = 0.023). A 40-gene exploratory set was defined as the 40 positive paired-effect genes with the strongest paired-test evidence in the same 13 pairs and used descriptively; its mean paired score difference was 1.02 z-score units, but no independent significance test was assigned to this within-cohort score. In the primary single-cell references, the set scored highest in Myeloid-like cells, providing cellular context without constituting a primary-recurrent single-cell comparison. TCGA-GBM showed a weak, non-significant baseline survival association (Cox HR 1.30, 95% CI 0.91-1.87, P = 0.15). A TMZ-resistant U251 derivative had a higher TMZ IC50 than parental cells (612 vs 89 µM), and Western blotting showed increased MGMT, CD44, Vimentin, HIF-1α, OPN and PD-L1 across three biological experiments. Together, these data provide a paired bulk description of recurrence-associated expression and use primary single-cell references only to localize the exploratory signal. - Source: PubMed
Publication date: 2026/09/19
Kong XuandongZhao MingJin QichaoPan Bolin - Gliomas, particularly glioblastoma, are characterized by profound molecular and cellular heterogeneity that drives tumor progression, therapeutic resistance, and poor clinical outcomes. Increasing evidence indicates that epigenetic deregulation, extending beyond genetic alterations, plays a central role in glioma initiation, evolution, and treatment response. This review summarizes current advances in the epigenetic landscape of adult gliomas with particular emphasis on the interplay between DNA methylation, histone modifications, chromatin remodeling and their contributions to molecular heterogeneity and precision neuro-oncology. We discuss key epigenetic mechanisms, including global DNA hypomethylation, promoter CpG island hypermethylation, histone acetylation and methylation and their effects on genome stability, transcriptional regulation, stemness, immune modulation, metabolic reprogramming, and therapeutic resistance. Clinically relevant biomarkers, including O6-methylguanine-DNA methyltransferase promoter methylation and the glioma CpG island methylator phenotype, are highlighted alongside emerging therapeutic targets such as histone deacetylases, Enhancer of Zeste Homologue 2, G9a, and protein arginine methyltransferase 5. We further examine the impact of spatial and temporal epigenetic heterogeneity on biomarker interpretation and treatment selection, as well as recent advances in methylation-based tumor classification. Collectively, this review highlights epigenetic deregulation as both a fundamental driver of adult glioma biology and a promising foundation for precision oncology. - Source: PubMed
Publication date: 2026/09/19
Gezer ElifcanCharkhian HamedTuncer Seref Bugra - Glioblastoma remains the most aggressive primary malignant brain tumor in adults. Disease progression is driven by multiple biological mechanisms, including glioma stem cell persistence, intratumoral heterogeneity, hypoxia-associated treatment resistance, enhanced DNA damage repair, immune evasion, and dynamic interactions within the tumor microenvironment. These factors contribute to therapeutic failure and highlight the need for novel treatment strategies and biomarker-driven approaches guiding patient selection and response assessment. Alpha particle therapy is a promising modality due to it's high linear energy transfer (LET), short tissue range, and potent relative biological effectiveness (RBE), inducing complex DNA damage that is difficult to repair while limiting radiation exposure to surrounding normal tissue. Among emerging platforms, Diffusing Alpha-emitters Radiation Therapy (Alpha DaRT) enables sustained intratumoral delivery of alpha-emitting radionuclides, while targeted alpha therapies employ tumor-specific radiopharmaceuticals to selectively deliver highly cytotoxic radiation to malignant cells. Beyond direct tumor cell killing, accumulating evidence suggests alpha particle therapy targets several biological pathways implicated in glioblastoma progression, including DNA damage response signaling, glioma stem cell survival, hypoxia-driven adaptation, and immune suppression. These mechanisms generated growing interest in the identification of predictive and pharmacodynamic biomarkers capable of guiding treatment selection and monitoring therapeutic response. Candidate biomarkers include DNA repair-associated proteins, stemness-related markers, molecular alterations such as MGMT and IDH status, liquid biopsy analytes, and advanced imaging biomarkers. In this review, we summarize current alpha-emitting therapeutic strategies for glioblastoma, with particular emphasis on Alpha DaRT, and discuss emerging biological mechanisms of response, biomarkers associated with tumor progression and therapeutic sensitivity, and opportunities for biomarker-guided clinical implementation. - Source: PubMed
Publication date: 2026/09/04
Kutuk TugceAtak EceHarrell MarshallRaval RajuBeyer SashaZhu SimengGrecula JohnFekrmandi FatemehMahase Sean SDibs KhaledTrifiletti DanielSingh RajElder James BradleyWu KyleGiglio PierreBlakaj Dukagjin MChakravarti ArnabPalmer Joshua - Gliomas are molecularly heterogeneous central nervous system tumors with marked variation in clinical outcome. Alzheimer's disease (AD)-associated transcriptional alterations may capture neural and immune programs relevant to glioma biology, but they do not by themselves establish a direct mechanistic relationship between AD and glioma. - Source: PubMed
Publication date: 2026/09/18
Junwu FuXiangqian RenChengyong YangDai KeWang JunXiang XinGuoqing Zhang - The study aimed to evaluate the performance of ultrasonographic medial gastrocnemius muscle thickness (MGMT) and pennation angle (MGMPA) in diagnosing sarcopenia among patients on maintenance hemodialysis (MHD). - Source: PubMed
Publication date: 2026/09/03
Yan MeilinAn WeiZhou LetingShan WeiweiZhang XiranDu AiyanZhang ZhijianWang Liang