ArticleCancer medicine2020
Methylome analyses of three glioblastoma cohorts reveal chemotherapy sensitivity markers within DDR genes.
Article in Cancer medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- High-grade astrocytoma with piloid features: A clinical and genomic analysis of prognostic factors using a large cohort.Neuro-oncology · 2026Article
- Diffuse astrocytoma, AYA-type, frequently MAPK-altered: report of 45 patients.Acta neuropathologica · 2025Article
- Hub Genes PRPF19 and PPIB: Molecular Pathways and Potential Biomarkers in COPD.International journal of chronic obstructive pulmonary disease · 2025Article
- DNA methylation heterogeneity attributable to a complex tumor immune microenvironment prompts prognostic risk in glioma.Epigenetics · 2024Article
- Mean global DNA methylation serves as independent prognostic marker in IDH-wildtype glioblastoma.Neuro-oncology · 2024Article
- The C250T Mutation ofCancers · 2024Article
- A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1.Nature communications · 2024Article
- Temporal change of DNA methylation subclasses between matched newly diagnosed and recurrent glioblastoma.Acta neuropathologica · 2024Article
- DNA methylation subclasses predict the benefit from gross total tumor resection in IDH-wildtype glioblastoma patients.Neuro-oncology · 2023Article
- Molecular landscapes of glioblastoma cell lines revealed a group of patients that do not benefit fromFrontiers in neuroscience · 2023Article
- Association of human telomerase reverse transcriptase promoter mutation with unfavorable prognosis in glioma: A systematic review and meta-analysis.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2023Review
- Comprehensive analyses indicated the association between m6A related long non-coding RNAs and various pathways in glioma.Cancer medicine · 2023Article
- Review
- Immune cell deconvolution of bulk DNA methylation data reveals an association with methylation class, key somatic alterations, and cell state in glial/glioneuronal tumors.Acta neuropathologica communications · 2021Article
- Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma.Nature communications · 2021Article
- Methylome analyses of three glioblastoma cohorts reveal chemotherapy sensitivity markers within DDR genes.Cancer medicine · 2020Article
- Molecular, histologic, and clinical characterization of methylation class pleomorphic xanthoastrocytoma: An analysis of 469 tumors.Neuro-oncology advancesArticle
- Unraveling glioblastoma diversity: Insights into methylation subtypes and spatial relationships.Neuro-oncology advancesArticle
- The promise of DNA damage response inhibitors for the treatment of glioblastoma.Neuro-oncology advancesReview
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Authors and funding
20 authors at 8 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGliomas evade current therapies through primary and acquired resistance and the effect of temozolomide is mainly restricted to methylguanin-O6-methyltransferase promoter (MGMT) promoter hypermethylated tumors. Further resistance markers are largely unknown and would help for better stratification.
methodsClinical data and methylation profiles from the NOA-08 (104, elderly glioblastoma) and the EORTC 26101 (297, glioblastoma) studies and 398 patients with glioblastoma from the Heidelberg Neuro-Oncology center have been analyzed focused on the predictive effect of DNA damage response (DDR) gene methylation. Candidate genes were validated in vitro.
resultsTwenty-eight glioblastoma 5'-cytosine-phosphat-guanine-3' (CpGs) from 17 DDR genes negatively correlated with expression and were used together with telomerase reverse transcriptase (TERT) promoter mutations in further analysis. CpG methylation of DDR genes shows highest association with the mesenchymal (MES) and receptor tyrosine kinase (RTK) II glioblastoma subgroup. MES tumors have lower tumor purity compared to RTK I and II subgroup tumors. CpG hypomethylation of DDR genes TP73 and PRPF19 correlated with worse patient survival in particular in MGMT promoter unmethylated tumors. TERT promoter mutation is most frequent in RTK I and II subtypes and associated with worse survival. Primary glioma cells show methylation patterns that resemble RTK I and II glioblastoma and long term established glioma cell lines do not match with glioblastoma subtypes. Silencing of selected resistance genes PRPF19 and TERT increase sensitivity to temozolomide in vitro.
conclusionHypomethylation of DDR genes and TERT promoter mutations is associated with worse tumor prognosis, dependent on the methylation cluster and MGMT promoter methylation status in IDH wild-type glioblastoma.
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