ArticleActa neuropathologica2015
Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment.
Article in Acta neuropathologica, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 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.
The trial behind it
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
106 citing papers in PubMed, 179 citations in OpenAlex.
- Trial
- Chemotherapy for adult low-grade gliomas: clinical outcomes by molecular subtype in a phase II study of adjuvant temozolomide.Neuro-oncology · 2017Trial
- MGMT promoter methylation across glioma subtypes: biological relevance, treatment response, and survival outcomes.Molecular biology reports · 2026Review
- Isocitrate Dehydrogenase-Mutant Astrocytomas: Risk Stratification and Therapeutic Advance.MedComm · 2026Review
- Clinicopathologic, molecular and tumor immune microenvironment features of mismatch repair-deficient glioblastomas in Lynch syndrome: a multicenter study of 29 cases with therapeutic implications.Acta neuropathologica communications · 2026Article
- KL-50: A novel therapeutic agent targeting MGMT-deficient glioblastoma.Neuro-oncology · 2025Article
- The molecular history of IDH-mutant astrocytomas without adjuvant treatment.Brain pathology (Zurich, Switzerland) · 2025Article
- Longitudinal multimodal profiling of IDH-wildtype glioblastoma reveals the molecular evolution and cellular phenotypes underlying prognostically different treatment responses.Neuro-oncology · 2025Article
- DNA damage response in brain tumors: A Society for Neuro-Oncology consensus review on mechanisms and translational efforts in neuro-oncology.Neuro-oncology · 2024Review
- Genetic and epigenetic instability as an underlying driver of progression and aggressive behavior in IDH-mutant astrocytoma.Acta neuropathologica · 2024Review
- Article
- Rise of oligodendroglioma hypermutator phenotype from a subclone harboring TP53 mutation after TMZ treatment.Brain tumor pathology · 2024Article
- IDH-mutant gliomas in children and adolescents - from biology to clinical trials.Frontiers in oncology · 2024Article
- "De novo replication repair deficient glioblastoma, IDH-wildtype" is a distinct glioblastoma subtype in adults that may benefit from immune checkpoint blockade.Acta neuropathologica · 2023Article
- Overcoming chemotherapy resistance in low-grade gliomas: A computational approach.PLoS computational biology · 2023Article
- A designer peptide against the EAG2-Kvβ2 potassium channel targets the interaction of cancer cells and neurons to treat glioblastoma.Nature cancer · 2023Article
- Molecular profiling of pre- and post-treatment pediatric high-grade astrocytomas reveals acquired increased tumor mutation burden in a subset of recurrences.Acta neuropathologica communications · 2023Article
- Expression and clinical significance of RBBP4 gene in lower-grade glioma: An integrative analysis.Biochemistry and biophysics reports · 2023Article
- Review
- DNA damage in IDH-mutant gliomas: mechanisms and clinical implications.Journal of neuro-oncology · 2023Review
46 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
24 authors at 8 institutions in 4 countries.
Funding
Abstract
Temozolomide (TMZ) increases the overall survival of patients with glioblastoma (GBM), but its role in the clinical management of diffuse low-grade gliomas (LGG) is still being defined. DNA hypermethylation of the O (6) -methylguanine-DNA methyltransferase (MGMT) promoter is associated with an improved response to TMZ treatment, while inactivation of the DNA mismatch repair (MMR) pathway is associated with therapeutic resistance and TMZ-induced mutagenesis. We previously demonstrated that TMZ treatment of LGG induces driver mutations in the RB and AKT-mTOR pathways, which may drive malignant progression to secondary GBM. To better understand the mechanisms underlying TMZ-induced mutagenesis and malignant progression, we explored the evolution of MGMT methylation and genetic alterations affecting MMR genes in a cohort of 34 treatment-naïve LGGs and their recurrences. Recurrences with TMZ-associated hypermutation had increased MGMT methylation compared to their untreated initial tumors and higher overall MGMT methylation compared to TMZ-treated non-hypermutated recurrences. A TMZ-associated mutation in one or more MMR genes was observed in five out of six TMZ-treated hypermutated recurrences. In two cases, pre-existing heterozygous deletions encompassing MGMT, or an MMR gene, were followed by TMZ-associated mutations in one of the genes of interest. These results suggest that tumor cells with methylated MGMT may undergo positive selection during TMZ treatment in the context of MMR deficiency.
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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.