The DOI matches its Crossref record; 86 of the 88 references it cites were found in a registry or an index.
Isocitrate Dehydrogenase 1 and 2 Mutations in Cancer: Alterations at a Crossroads of Cellular Metabolism
Open accessAbstract
Dysregulation of metabolism is a common phenomenon in cancer cells. The NADP(+)-dependent isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) function at a crossroads of cellular metabolism in lipid synthesis, cellular defense against oxidative stress, oxidative respiration, and oxygen-sensing signal transduction. We review the normal functions of the encoded enzymes, frequent mutations of IDH1 and IDH2 recently found in human cancers, and possible roles for the mutated enzymes in human disease. IDH1 and IDH2 mutations occur frequently in some types of World Health Organization grades 2-4 gliomas and in acute myeloid leukemias with normal karyotype. IDH1 and IDH2 mutations are remarkably specific to codons that encode conserved functionally important arginines in the active site of each enzyme. To date, all IDH1 mutations have been identified at the Arg132 codon. Mutations in IDH2 have been identified at the Arg140 codon, as well as at Arg172, which is aligned with IDH1 Arg132. IDH1 and IDH2 mutations are usually heterozygous in cancer, and they appear to confer a neomorphic enzyme activity for the enzymes to catalyze the production of D-2-hydroxyglutarate. Study of alterations in these metabolic enzymes may provide insights into the metabolism of cancer cells and uncover novel avenues for development of anticancer therapeutics.
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“There is a renewed interest in the area of cancer metabolism with metabolic reprogramming coined as a hallmark of cancer based on the discovery of mutations and alterations in IDH1 and IDH2 along with succinate dehydrogenase (SDH), fumarate hydratase (FH), and pyruvate kinase M2 (PKM2) [41, 42].”
From Modeling APC mutagenesis and familial adenomatous polyposis using human iPS cells (2018) · cites this paper as [42]
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Self-citationIDH1 and IDH2 Mutations in Gliomas
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Self-citationCancer-associated IDH1 mutations produce 2-hydroxyglutarate
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Research works printed but not linked: 7
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Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
“Although these mutations may prove to have been clonally selected for their ability to alter energy metabolism, there is confounding data associating their activity with elevated oxidation and stability of the HIF-1 transcription factors (Reitman and Yan, 2010), which could in turn affect genome stability and angiogen…”
Otto Warburg's contributions to current concepts of cancer metabolism
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“Heterozygous mutations in either of the two isoforms of the Krebscycle enzyme isocitrate dehydrogenase (IDH1/2) occur with a high prevalence in glioma, malignant glioblastoma and acute myeloid leukaemia (Dang et al, 2010; Reitman & Yan, 2010).”
BackgroundMetabolic targets for cancer therapy
Galluzzi, L., Kepp, O., Heiden, M. G. V., & Kroemer, G. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4145 · Cited by 731
Metadata
- Authors
- Reitman, Z. J., & Yan, H.
- Affiliations
- Duke University (US)
- Venue
- JNCI Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-05-31
- Volume
- 102
- Issue
- 13
- Pages
- 932-941
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- PMC
- PMC2897878
- OpenAlex
- W2124951199
- Cited by
- 562
- References
- 88
- Citations by year
- 2026: 22 · 2025: 41 · 2024: 20 · 2023: 33 · 2022: 31 · 2021: 44 · 2020: 40 · 2019: 43 · 2018: 40 · 2017: 36 · 2016: 31 · 2015: 34 · 2014: 28 · 2013: 34 · 2012: 38
- FWCI
- 3.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Cancer Institute (R01CA118822, R01CA140316)
- National Institute of General Medical Sciences (T32GM007171)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
- Keywords
- IDH1, IDH2, IDH1 mutation, IDH2 mutation, cancer metabolism, glioma, acute myeloid leukemia, D-2-hydroxyglutarate, oxidative stress, lipogenesis, oxygen sensing, anticancer agents
- MeSH terms
- Animals, Hypoxia, Arginine, Brain Neoplasms, Codon, Glioblastoma, Glucose, Glutarates, Humans, Isocitrate Dehydrogenase, Mutation, NADP, Neoplasms, Oligodendroglioma, Oncogenes, Signal Transduction, Up-Regulation, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor
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