The DOI matches its Crossref record; 28 of the 30 references it cites were found in a registry or an index.
IDH1 and IDH2 Mutations in Gliomas
Open accessAbstract
BACKGROUND: A recent genomewide mutational analysis of glioblastomas (World Health Organization [WHO] grade IV glioma) revealed somatic mutations of the isocitrate dehydrogenase 1 gene (IDH1) in a fraction of such tumors, most frequently in tumors that were known to have evolved from lower-grade gliomas (secondary glioblastomas). METHODS: We determined the sequence of the IDH1 gene and the related IDH2 gene in 445 central nervous system (CNS) tumors and 494 non-CNS tumors. The enzymatic activity of the proteins that were produced from normal and mutant IDH1 and IDH2 genes was determined in cultured glioma cells that were transfected with these genes. RESULTS: We identified mutations that affected amino acid 132 of IDH1 in more than 70% of WHO grade II and III astrocytomas and oligodendrogliomas and in glioblastomas that developed from these lower-grade lesions. Tumors without mutations in IDH1 often had mutations affecting the analogous amino acid (R172) of the IDH2 gene. Tumors with IDH1 or IDH2 mutations had distinctive genetic and clinical characteristics, and patients with such tumors had a better outcome than those with wild-type IDH genes. Each of four tested IDH1 and IDH2 mutations reduced the enzymatic activity of the encoded protein. CONCLUSIONS: Mutations of NADP(+)-dependent isocitrate dehydrogenases encoded by IDH1 and IDH2 occur in a majority of several types of malignant gliomas.
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In the citing paper
“Recurrent somatic point mutations in the genes coding for isocitrate dehydrogenase 1 and 2 (IDH1, IDH2) are found in a wide variety of cancers, including glioblastoma multiforme (GBM) (Yan et al., 2009) and acute myeloid leukemia (AML) (Dang et al., 2016; Mardis et al., 2009).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Yan et al., 2009
In the citing paper
“Both IDH1 R132 and IDH2 R172 mutants lack the wild-type enzyme’s ability to convert isocitrate to α-ketoglutarate”
From The Common Feature of Leukemia-Associated IDH1 and IDH2 Mutations Is a Neomorphic Enzyme Activity Converting α-Ketoglutarate to 2-Hydroxyglutarate (2010) · cites this paper as Yan et al., 2009
In the citing paper
“Mutations in human cytosolic isocitrate dehydrogenase I (IDH1) occur somatically in >70% of grade II-III gliomas and secondary glioblastomas, and in 8.5% of acute myeloid leukemias (AML)”
From The Common Feature of Leukemia-Associated IDH1 and IDH2 Mutations Is a Neomorphic Enzyme Activity Converting α-Ketoglutarate to 2-Hydroxyglutarate (2010) · cites this paper as Yan et al., 2009
In the citing paper
“This is consistent with data presented here that IDH1-mutated and IDH2-mutated AML samples typically do not harbor other known mutations associated with AML, as well as a prior report that IDH-mutated gliomas often lack other mutations that are commonly acquired early in glioma pathogenesis (Yan et al., 2009).”
From The Common Feature of Leukemia-Associated IDH1 and IDH2 Mutations Is a Neomorphic Enzyme Activity Converting α-Ketoglutarate to 2-Hydroxyglutarate (2010) · cites this paper as Yan et al., 2009
In the citing paper
“Monoallelic mutation of the same residue in IDH1, or the analogous residue in the related enzyme IDH2, is a common feature of gliomas as more than 80% of indolent gliomas harbor such a mutation (28, 29).”
From Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation (2009) · cites this paper as [29]
In the citing paper
“The IDH genes (IDH1 and IDH2) encode isocitrate dehydrogenases, and mutations in these genes are among the most frequent found in diffuse gliomas118,119.”
From Transcription factors as readers and effectors of DNA methylation (2016) · cites this paper as [119]
In the citing paper
“These “oncohistones” are found almost exclusively in pHGG and are mutually exclusive with the recurrent mutations in isocitrate dehydrogenase enzymes (IDH) identified in young adult gliomas”
From H3.3K27M Cooperates with Trp53 Loss and PDGFRA Gain in Mouse Embryonic Neural Progenitor Cells to Induce Invasive High-Grade Gliomas (2017) · cites this paper as Yan et al., 2009
In the citing paper
“IDH1/2 mutations have been identified in a range of tumor types, including solid tumors (e.g., gliomas and chondrosarcomas) and blood cancers like acute myelogenous leukemia (169, 170, 171).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [171]
In the citing paper
“a small fraction of gliomas lacking IDH1 mutations were known to harbor mutations at IDH2 R172, the analogous residue to IDH1 R132 (Yan et al., 2009)”
From Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate (2012) · cites this paper as Yan et al., 2009
In the citing paper
“Genomic sequencing of gliomas (Parsons et al., 2008; Yan et al., 2009) and acute myelogenous leukemia (Mardis et al., 2009) identified mutations in two isoforms of NADP+-dependent isocitrate dehydrogenase (IDH1 and IDH2).”
From Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us? (2012) · cites this paper as Yan et al., 2009
In the citing paper
“the presence of IDH1/2 mutations in gliomas is associated with both lower histological grade and a slower rate of disease progression”
From Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us? (2012) · cites this paper as Yan et al., 2009
In the citing paper
“Furthermore, TH17 cell differentiation could be initiated by exogenous addition of D-2-HG to naïve CD4+ T cells or by genetic silencing of TET1 and TET2, established targets of 2-HG143-145.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [143]
In the citing paper
“The elevated levels of D-2-HG was associated with increased DNA methylation levels at the Foxp3 locus, the master transcription factor driving iTreg differentiation, resulting in its repression143.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [143]
In the citing paper
“Inhibition of GOT1 by aminooxyacetic acid (AOAA), which decreases D-2-HG levels, promoted expression Foxp3 and the differentiation of TH17 cells to iTregs143.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [143]
In the citing paper
“On the other hand, induced regulatory T (iTreg) cells, also derived from naïve CD4+ T cells, do not require HIF-1α143,146.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [143]
In the citing paper
“T-helper 17 (TH17) cells, derived from naïve CD4+ T cells, are one such subset that rely heavily on a switch from OXPHOS to glycolysis, a process that requires the activation of HIF-1α and induction of RORγt143,146.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [143]
In the citing paper
“Lastly, AOAA ameliorated disease progression in EAE, a disease in which TH17 cells mediate pathology143.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [143]
In the citing paper
“Interestingly, Xu and colleagues (2017) observed increased levels in of D-2-HG in TH17 cells, when compared to iTreg cells143.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [143]
In the citing paper
“Mechanistically, D-2-HG production was driven by the conversion of glutamate to α-KG by the aspartate aminotransferase GOT1.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [143]
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Metadata
- Authors
- Yan, H., Parsons, D. W., Jin, G., McLendon, R., Rasheed, B. A., Yuan, W., Kos, I., Batinic-Haberle, I., Jones, S., Riggins, G. J., Friedman, H., Friedman, A., Reardon, D., Herndon, J., Kinzler, K. W., Velculescu, V. E., Vogelstein, B., & Bigner, D. D.
- Affiliations
- Duke University (US)
- Howard Hughes Medical Institute (US)
- Pediatric Brain Tumor Foundation (US)
- United States Food and Drug Administration (US)
- Johns Hopkins University (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2009-02-19
- Volume
- 360
- Issue
- 8
- Pages
- 765-773
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC2820383
- OpenAlex
- W2126817554
- Cited by
- 5,847
- References
- 30
- Citations by year
- 2026: 168 · 2025: 256 · 2024: 330 · 2023: 367 · 2022: 397 · 2021: 481 · 2020: 496 · 2019: 374 · 2018: 398 · 2017: 369 · 2016: 296 · 2015: 340 · 2014: 350 · 2013: 336 · 2012: 322
- FWCI
- 139.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01ca121113-15, 5p50ns020023-30)
- University of California, Los Angeles
- National Cancer Institute (5R37 CA11898, 2 P30 CA 14236, R37CA011898, R01CA118822, CA 57345, R01-CA121113, CA-121113, CA43460, R37CA043460, R01CA057345, R37CA11898-34, P50CA108786, R01CA140316, P50CA062924, R37CA057345, P30CA014236)
- National Institute of Neurological Disorders and Stroke (P50-NS020023, NS20023-21, 5P50NS20023)
- Topics
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- IDH1 mutation, IDH2 mutation, isocitrate dehydrogenase, glioma, glioblastoma, astrocytoma, oligodendroglioma, secondary glioblastoma, NADP-isocitrate dehydrogenase, enzyme activity, patient outcomes
- MeSH terms
- Adult, Astrocytoma, Brain Neoplasms, DNA Mutational Analysis, Glioblastoma, Glioma, Humans, Isocitrate Dehydrogenase, Mutation, Neoplasms, Oligodendroglioma, Tumor Cells, Cultured, Disease Progression, Kaplan-Meier Estimate, Young Adult
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