ArticleNeuro-oncology2019
Intratumor DNA methylation heterogeneity in glioblastoma: implications for DNA methylation-based classification.
Article in Neuro-oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 2 of them syntheses that pooled it.
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Who cites it
76 citing papers in PubMed, 2 syntheses or guidelines pooled it, 134 citations in OpenAlex.
- A systematic review of high impact CpG sites and regions for MGMT methylation in glioblastoma [A systematic review of MGMT methylation in GBM].BMC neurology · 2024Pooled it
- Epigenetic Underpinnings of Inflammation: A Key to Unlock the Tumor Microenvironment in Glioblastoma.Frontiers in immunology · 2022Pooled it
- MGMT promoter methylation as a molecular biomarker in neuro-oncology: current practices, challenges, and future directions.Journal of neuro-oncology · 2026Review
- Quantitative stability of MGMT promoter methylation in recurrent glioma and implications for temozolomide rechallenge.Journal of neuro-oncology · 2026Article
- Human Blood-Brain Tumor Barrier on a Chip to Investigate Personalized Treatment for Glioblastoma Patients.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Methylation profiling and alternative classification approaches in a glioma-enriched FFPE stereotaxic biopsy cohort.Acta neuropathologica communications · 2026Article
- Hetairos is a histology-based artificial intelligence model for predicting central nervous system tumor methylation subtypes.Nature cancer · 2026Article
- DNA methylation heterogeneity in complex tumor microenvironment: Quantitative methods, influencing factors, and clinical implications.Genes & diseases · 2026Review
- cIMPACT-NOW update 11: Proposal on adaptation of diagnostic criteria for IDH- and H3-wildtype diffuse high-grade gliomas and for posterior fossa ependymal tumors.Brain pathology (Zurich, Switzerland) · 2026Article
- Integration of omics data in the diagnosis and therapy of glioblastoma.Brain pathology (Zurich, Switzerland) · 2026Review
- Magnetic susceptibility properties of tumor-associated cells imaged by MRI reveal glioblastoma infiltration in the edema region.Communications medicine · 2025Article
- GLIMMER: an interim subgroup analysis from an ongoing prospective study evaluating hyperspectral imaging for MGMT promoter methylation in gliomas.Journal of neuro-oncology · 2025Observational
- Prospective, multicenter validation of a platform for rapid molecular profiling of central nervous system tumors.Nature medicine · 2025Article
- DNA methylation heterogeneity attributable to a complex tumor immune microenvironment prompts prognostic risk in glioma.Epigenetics · 2024Article
- Analysis of DNA Methylation in Gliomas: Assessment of Preanalytical Variables.Laboratory investigation; a journal of technical methods and pathology · 2024Article
- An expanded view of cell competition.Development (Cambridge, England) · 2024Review
- Review
- Genetic and epigenetic instability as an underlying driver of progression and aggressive behavior in IDH-mutant astrocytoma.Acta neuropathologica · 2024Review
- UCHL3 induces radiation resistance and acquisition of mesenchymal phenotypes by deubiquitinating POLD4 in glioma stem cells.Cellular and molecular life sciences : CMLS · 2024Article
- Temporal change of DNA methylation subclasses between matched newly diagnosed and recurrent glioblastoma.Acta neuropathologica · 2024Article
16 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
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA feature of glioblastoma (GBM) is cellular and molecular heterogeneity, both within and between tumors. This variability causes a risk for sampling bias and potential tumor escape from future targeted therapy. Heterogeneous intratumor gene expression in GBM is well documented, but little is known regarding the epigenetic heterogeneity. Variability in DNA methylation within tumors would have implications for diagnostics, as methylation can be used for tumor classification, subtyping, and determination of the clinically used biomarker O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. We therefore aimed to profile the intratumor DNA methylation heterogeneity in GBM and its effect on diagnostic properties.
methodsThree to 4 spatially separated biopsies per tumor were collected from 12 GBM patients. We performed genome-wide DNA methylation analysis and investigated intratumor variation.
resultsAll samples were classified as GBM isocitrate dehydrogenase (IDH) wild type (wt)/mutated by methylation profiling, but the subclass differed within 5 tumors. Some GBM samples exhibited higher DNA methylation differences within tumors than between, and many cytosine-phosphate-guanine (CpG) sites (mean: 17 000) had different methylation levels within the tumors. MGMT methylation status differed in IDH mutated patients (1/1).
conclusionsWe demonstrated that intratumor DNA methylation heterogeneity is a feature of GBM. Although all biopsies were classified as GBM IDH wt/mutated by methylation analysis, the assigned subclass differed in samples from the same patient. The observed heterogeneity within tumors is important to consider for methylation-based biomarkers and future improvements in stratification of GBM patients.
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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.