ArticleGenome research2012
A heterozygous IDH1R132H/WT mutation induces genome-wide alterations in DNA methylation.
Article in Genome research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 1 of them a synthesis that pooled it.
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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
121 citing papers in PubMed, 1 synthesis or guideline pooled it, 180 citations in OpenAlex.
- Meta-analysis of IDH-mutant cancers identifies EBF1 as an interaction partner for TET2.Nature communications · 2013Pooled it
- The DNA methylome of DDR genes and benefit from RT or TMZ in IDH mutant low-grade glioma treated in EORTC 22033.Acta neuropathologica · 2018Trial
- Review
- Recent Advances in Targeted Therapies for Adult Gliomas.Current neurology and neuroscience reports · 2026Review
- Mitochondrial targets in IDH1-mutated cholangiocarcinoma.Hepatology communications · 2026Review
- Glioblastoma at the crossroads: current understanding and future therapeutic horizons.Signal transduction and targeted therapy · 2025Review
- Understanding the Radiobiology of Central Nervous System Diseases in the Golden Age of Radiosurgery-Does It Matter?Brain sciences · 2025Review
- Catalytically distinct metabolic enzyme isocitrate dehydrogenase 1 mutants tune phenotype severity in tumor models.The Journal of biological chemistry · 2025Article
- Mechanism analysis and targeted therapy of IDH gene mutation in glioma.American journal of cancer research · 2025Review
- Spectrum of IDH-mutant tumors in Ollier-Maffucci disease: the triple interaction theory.Orphanet journal of rare diseases · 2024Article
- Metabolic regulation of the glioblastoma stem cell epitranscriptome by malate dehydrogenase 2.Cell metabolism · 2024Article
- DNA methylation and gene expression as determinants of genome-wide cell-free DNA fragmentation.Nature communications · 2024Article
- Associations in cell type-specific hydroxymethylation and transcriptional alterations of pediatric central nervous system tumors.Nature communications · 2024Article
- RapidBiology methods & protocols · 2024Article
- Brain Tumors: Development, Drug Resistance, and Sensitization - An Epigenetic Approach.Epigenetics · 2023Review
- Variant allelic frequencies of driver mutations can identify gliomas with potentially false-negative MGMT promoter methylation results.Acta neuropathologica communications · 2023Article
- Review
- Review
- Hydroxymethylation alterations in progenitor-like cell types of pediatric central nervous system tumors are associated with cell type-specific transcriptional changes.Research square · 2023Article
- Nanomechanical Signatures in Glioma Cells Depend on CD44 Distribution in IDH1 Wild-Type but Not in IDH1R132H Mutant Early-Passage Cultures.International journal of molecular sciences · 2023Article
61 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
10 authors at 4 institutions in 1 country.
Funding
Abstract
Monoallelic point mutations of the NADP(+)-dependent isocitrate dehydrogenases IDH1 and IDH2 occur frequently in gliomas, acute myeloid leukemias, and chondromas, and display robust association with specific DNA hypermethylation signatures. Here we show that heterozygous expression of the IDH1(R132H) allele is sufficient to induce the genome-wide alterations in DNA methylation characteristic of these tumors. Using a gene-targeting approach, we knocked-in a single copy of the most frequently observed IDH1 mutation, R132H, into a human cancer cell line and profiled changes in DNA methylation at over 27,000 CpG dinucleotides relative to wild-type parental cells. We find that IDH1(R132H/WT) mutation induces widespread alterations in DNA methylation, including hypermethylation of 2010 and hypomethylation of 842 CpG loci. We demonstrate that many of these alterations are consistent with those observed in IDH1-mutant and G-CIMP+ primary gliomas and can segregate IDH wild-type and mutated tumors as well as those exhibiting the G-CIMP phenotype in unsupervised analysis of two primary glioma cohorts. Further, we show that the direction of IDH1(R132H/WT)-mediated DNA methylation change is largely dependent upon preexisting DNA methylation levels, resulting in depletion of moderately methylated loci. Additionally, whereas the levels of multiple histone H3 and H4 methylation modifications were globally increased, consistent with broad inhibition of histone demethylation, hypermethylation at H3K9 in particular accompanied locus-specific DNA hypermethylation at several genes down-regulated in IDH1(R132H/WT) knock-in cells. These data provide insight on epigenetic alterations induced by IDH1 mutations and support a causal role for IDH1(R132H/WT) mutants in driving epigenetic instability in human cancer cells.
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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.