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Isocitrate dehydrogenase-1 mutations: a fundamentally new understanding of diffuse glioma?
Abstract
The discovery of somatic mutations in the gene encoding isocitrate dehydrogenase-1 (IDH1) in glioblastomas was remarkable because the enzyme was not previously identified with any known oncogenic pathway. IDH1 is mutated in up to 75% of grade II and grade III diffuse gliomas. Apart from acute myeloid leukaemia, other tumour types do not carry IDH1 mutations. Mutations in a homologous gene, IDH2, have also been identified, although they are much rarer. Although TP53 mutations and 1p/19q codeletions are mutually exclusive in gliomas, in both of these genotypes IDH1 mutations are common. IDH1 and IDH2 mutations are early events in the development of gliomas. Moreover, IDH1 and IDH2 mutations are a major prognostic marker for overall and progression-free survival in grade II-IV gliomas. Mutated IDH1 has an altered catalytic activity that results in the accumulation of 2-hydroxyglutarate. Molecularly, IDH1 and IDH2 mutations are heterozygous, affect only a single codon, and rarely occur together. Because IDH1 does not belong to a traditional oncogenic pathway and is specifically and commonly mutated in gliomas, the altered enzymatic activity of IDH1 may provide a fundamentally new understanding of diffuse glioma.
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“One of the key molecular differences between primary and secondary glioblastoma is the presence of isocitrate dehydrogenase-1 (IDH1) mutations which are found in approximately 75% of secondary GBM but are rare in primary GBM [13].”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [13]
In the citing paper
“In contrast to wt-p53, GOF mut-p53 exhibits interactions with distinct transcription factors (e.g., NF-ɣ, SREBP, VDR, Sp1, ETS2, NFR2, p73, p63) that promote tumor initiation and progression [13,72,73,74,75,76,77].”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [13]
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Metadata
- Authors
- Kloosterhof, N. K., Bralten, L. B., Dubbink, H. J., French, P. J., & van den Bent, M. J.
- Affiliations
- Erasmus MC - Sophia Children’s Hospital (NL)
- Daniel den Hoed Kliniek (NL)
- Erasmus MC (NL)
- Venue
- The Lancet Oncology
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 12
- Issue
- 1
- Pages
- 83-91
- ISSN
- 1470-2045 (ISSN-L)
- OpenAlex
- W2084945856
- Cited by
- 222
- References
- 86
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 10 · 2023: 6 · 2022: 12 · 2021: 19 · 2020: 21 · 2019: 10 · 2018: 11 · 2017: 12 · 2016: 12 · 2015: 17 · 2014: 19 · 2013: 20 · 2012: 17
- FWCI
- 2.36
- Type
- journal article
- Language
- en
- Update notices
- erratum (2010-10-01)
- Open access
- closed
- Locations
- The Lancet Oncology (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- IDH1, IDH1 mutation, IDH2 mutation, diffuse glioma, glioblastoma, 2-hydroxyglutarate, TP53 mutation, 1p/19q codeletion, prognostic factors, tumor progression, oncogenic signaling
- MeSH terms
- Brain Neoplasms, Codon, Glioma, Humans, Isocitrate Dehydrogenase, Mutation
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