ArticleJournal of neuro-oncology2009
Evaluation of MGMT promoter methylation status and correlation with temozolomide response in orthotopic glioblastoma xenograft model.
Article in Journal of neuro-oncology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
64 citing papers in PubMed, 97 citations in OpenAlex.
- Targeting the NAD+ Salvage Pathway Blocks Metabolic Recovery and Enhances β-Lapachone Toxicity in NQO1-Expressing Glioblastoma Cells.Cancer research communications · 2026Article
- MGMT promoter methylation across glioma subtypes: biological relevance, treatment response, and survival outcomes.Molecular biology reports · 2026Review
- The Size of Glioblastoma Spheroids Influences Patterns of Invasion and Temozolomide Efficacy.Tissue engineering. Part C, Methods · 2026Article
- Biodegradable nanofibrous scaffolds enhance standard of care for glioblastoma via localized targeted therapy.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Size-dependent invasion and therapeutic phenotype of 42MGBA glioblastoma spheroids.bioRxiv : the preprint server for biology · 2025Article
- Personalising glioblastoma medicine: explant organoid applications, challenges and future perspectives.Acta neuropathologica communications · 2025Review
- Harnessing immunotherapy: cancer vaccines as novel therapeutic strategies for brain tumor.Frontiers in immunology · 2025Review
- XPO1-inhibitor Selinexor induces MGMT expression by activating PKA-CREB signaling inFrontiers in oncology · 2025Article
- Two decades of progress in glioma methylation research: the rise of temozolomide resistance and immunotherapy insights.Frontiers in neuroscience · 2024Article
- Molecular characterization of Richter syndrome identifies de novo diffuse large B-cell lymphomas with poor prognosis.Nature communications · 2023Article
- The University of California San Francisco Preoperative Diffuse Glioma MRI Dataset.Radiology. Artificial intelligence · 2022Article
- Glioblastoma, from disease understanding towards optimal cell-based in vitro models.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Clinically relevant orthotopic xenograft models of patient-derived glioblastoma in zebrafish.Disease models & mechanisms · 2022Article
- Contemporary Mouse Models in Glioma Research.Cells · 2021Review
- The Tumor SuppressorCancers · 2021Article
- siRNA nanoparticle suppresses drug-resistant gene and prolongs survival in an orthotopic glioblastoma xenograft mouse model.Advanced functional materials · 2021Article
- Novel dopamine receptor 3 antagonists inhibit the growth of primary and temozolomide resistant glioblastoma cells.PloS one · 2021Article
- OBMC cancer · 2020Article
- Phenotypic selection through cell death: stochastic modelling of O-6-methylguanine-DNA methyltransferase dynamics.Royal Society open science · 2020Article
- Genomic and Phenotypic Characterization of a Broad Panel of Patient-Derived Xenografts Reflects the Diversity of Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
CpG methylation within the O6-methylguanine-DNA-methyltransferase (MGMT) promoter is associated with enhanced survival of glioblastoma multiforme (GBM) patients treated with temozolomide (TMZ). Although MGMT promoter is methylated in approximately 50% of GBM, several studies have reported a lack of correlation between MGMT methylation and protein expression levels and consequently inaccurate discrimination of TMZ sensitive and resistant patients. To understand the limitations of currently used assays, TMZ responsiveness of 13 GBM xenograft lines was correlated with MGMT protein expression and MGMT promoter methylation determined by (1) standard methylation-specific polymerase chain reaction (MS-PCR), (2) quantitative MS-PCR (qMS-PCR), and (3) bisulfite sequencing. For each xenograft line, mice with established intracranial xenografts were treated with vehicle control or TMZ (66 mg/kgx5 days), and TMZ response was defined as relative prolongation in median survival for TMZ-treated versus control-treated mice. The relative survival benefit with TMZ was inversely related to MGMT protein expression (r=-0.75; P=0.003) and directly correlated with qMS-PCR (r=0.72; P=0.006). There was a direct correlation between MGMT methylation signal by qMS-PCR and the number of methylated CpG sites within the region amplified by MS-PCR (r=0.78, P=0.002). However, bisulfite sequencing revealed heterogeneity in the extent of CpG methylation in those tumors with a robust qMS-PCR signal. Three of the 4 GBM lines with a qMS-PCR signal greater than 10% had at least 1 unmethylated CpG site, while only one line was fully methylated at all 12 CpG sites. These data highlight one potential limitation of the evaluation of MGMT methylation by MS-PCR assay and suggest that more detailed evaluation of methylation at individual CpG sites relative to TMZ response may be worth pursuing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.