ArticleESMO open2022
Methylation subgroup and molecular heterogeneity is a hallmark of glioblastoma: implications for biopsy targeting, classification and therapy.
Article in ESMO open, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Receptor tyrosine kinase targeted therapies in glioblastoma: a systematic review.Frontiers in medicine · 2026Pooled it
- MGMT promoter methylation across glioma subtypes: biological relevance, treatment response, and survival outcomes.Molecular biology reports · 2026Review
- MGMT promoter methylation status for glioblastoma: defining the clinically relevant cut-off value for pyrosequencing.Journal of neuro-oncology · 2026Article
- MixBranchNet: a task-adaptive network for glioma segmentation and genotype prediction by exploiting spatial-spectral correlations in CEST MRI.Frontiers in oncology · 2026Article
- Personalized chronotherapy in glioblastoma: integrating circadian profiling and PK-PD modelling to optimize temozolomide timing.NPJ precision oncology · 2025Article
- Epigenetic Alterations in Glioblastoma Multiforme as Novel Therapeutic Targets: A Scoping Review.International journal of molecular sciences · 2025Article
- Adjuvant therapy guided by molecular classification in endometrial cancer: survival benefit and safety profile.American journal of translational research · 2025Article
- Analysis of DNA Methylation in Gliomas: Assessment of Preanalytical Variables.Laboratory investigation; a journal of technical methods and pathology · 2024Article
- Resolving spatial response heterogeneity in glioblastoma.European journal of nuclear medicine and molecular imaging · 2024Article
- Review
- Genetic and epigenetic instability as an underlying driver of progression and aggressive behavior in IDH-mutant astrocytoma.Acta neuropathologica · 2024Review
- Variant allelic frequencies of driver mutations can identify gliomas with potentially false-negative MGMT promoter methylation results.Acta neuropathologica communications · 2023Article
- Utility of genome-wide DNA methylation profiling for pediatric-type diffuse gliomas.Brain tumor pathology · 2023Review
- Review
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIntratumoral heterogeneity at the cellular and molecular level is a hallmark of glioblastoma (GB) that contributes to treatment resistance and poor clinical outcome. Little is known regarding epigenetic heterogeneity and intratumoral phylogeny and their implication for molecular classification and targeted therapies. PATIENTS AND
methodsMultiple tissue biopsies (238 in total) were sampled from 56 newly-diagnosed, treatment-naive GB patients from a prospective in-house cohort and publicly available data and profiled for DNA methylation using the Illumina MethylationEPIC array. Methylation-based classification using the glioma classifier developed by Ceccarelli et al. and estimation of the MGMT promoter methylation status via the MGMT-STP27 model were carried out. In addition, copy number variations (CNVs) and phylogeny were analyzed.
resultsAlmost half of the patients (22/56, 39%) harbored tumors composed of heterogeneous methylation subtypes. We found two predominant subtype combinations: classic-/mesenchymal-like, and mesenchymal-/pilocytic astrocytoma-like. Nine patients (16%) had tumors composed of subvolumes with and without MGMT promoter methylation, whereas 20 patients (36%) were homogeneously methylated, and 27 patients (48%) were homogeneously unmethylated. CNV analysis revealed high variations in many genes, including CDKN2A/B, EGFR, and PTEN. Phylogenetic analysis correspondingly showed a general pattern of CDKN2A/B loss and gain of EGFR, PDGFRA, and CDK4 during early stages of tumor development.
conclusions(Epi)genetic intratumoral heterogeneity is a hallmark of GB, both at DNA methylation and CNV level. This intratumoral heterogeneity is of utmost importance for molecular classification as well as for defining therapeutic targets in this disease, as single biopsies might underestimate the true molecular diversity in a tumor.
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