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- Publisher Website: 10.1158/2159-8290.CD-13-0083
- Scopus: eid_2-s2.0-84880300456
- PMID: 23796461
- WOS: WOS:000321615600021
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Article: Oncogenic isocitrate dehydrogenase mutations: Mechanisms, models, and clinical opportunities
Title | Oncogenic isocitrate dehydrogenase mutations: Mechanisms, models, and clinical opportunities |
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Authors | |
Issue Date | 2013 |
Citation | Cancer Discovery, 2013, v. 3, n. 7, p. 730-741 How to Cite? |
Abstract | Heterozygous mutations in catalytic arginine residues of isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are common in glioma, acute myeloid leukemia, chondrosarcoma, cholangiocarcinoma, and angioimmunoblastic T-cell lymphoma. The mutant enzymes acquire a neomorphic activity that converts α-ketoglutarate (α-KG) to D-2-hydroxyglutarate (D2HG), a rare metabolite. In cells and tissues expressing mutant IDH, D2HG concentrations are highly elevated. D2HG may act as an "oncometabolite" by inhibiting a class of α-KG-dependent enzymes involved in epigenetic regulation, collagen synthesis, and cell signaling. Knock-in mouse models of IDH1 mutations have shed light on these mechanisms and will provide valuable animal models for further investigation. Significance: Mutations in IDH1 and IDH2 promote the development of a number of malignancies. These active site mutations cause a gain-of-function leading to the accumulation of the rare metabolite D2HG. Mouse models of these mutations should provide insights into the mechanisms driving tumorigenesis and facilitate evaluation of new treatments. © 2013 American Association for Cancer Research. |
Persistent Identifier | http://hdl.handle.net/10722/292762 |
ISSN | 2023 Impact Factor: 29.7 2023 SCImago Journal Rankings: 7.533 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Cairns, Rob A. | - |
dc.contributor.author | Mak, Tak W. | - |
dc.date.accessioned | 2020-11-17T14:57:10Z | - |
dc.date.available | 2020-11-17T14:57:10Z | - |
dc.date.issued | 2013 | - |
dc.identifier.citation | Cancer Discovery, 2013, v. 3, n. 7, p. 730-741 | - |
dc.identifier.issn | 2159-8274 | - |
dc.identifier.uri | http://hdl.handle.net/10722/292762 | - |
dc.description.abstract | Heterozygous mutations in catalytic arginine residues of isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are common in glioma, acute myeloid leukemia, chondrosarcoma, cholangiocarcinoma, and angioimmunoblastic T-cell lymphoma. The mutant enzymes acquire a neomorphic activity that converts α-ketoglutarate (α-KG) to D-2-hydroxyglutarate (D2HG), a rare metabolite. In cells and tissues expressing mutant IDH, D2HG concentrations are highly elevated. D2HG may act as an "oncometabolite" by inhibiting a class of α-KG-dependent enzymes involved in epigenetic regulation, collagen synthesis, and cell signaling. Knock-in mouse models of IDH1 mutations have shed light on these mechanisms and will provide valuable animal models for further investigation. Significance: Mutations in IDH1 and IDH2 promote the development of a number of malignancies. These active site mutations cause a gain-of-function leading to the accumulation of the rare metabolite D2HG. Mouse models of these mutations should provide insights into the mechanisms driving tumorigenesis and facilitate evaluation of new treatments. © 2013 American Association for Cancer Research. | - |
dc.language | eng | - |
dc.relation.ispartof | Cancer Discovery | - |
dc.title | Oncogenic isocitrate dehydrogenase mutations: Mechanisms, models, and clinical opportunities | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1158/2159-8290.CD-13-0083 | - |
dc.identifier.pmid | 23796461 | - |
dc.identifier.scopus | eid_2-s2.0-84880300456 | - |
dc.identifier.volume | 3 | - |
dc.identifier.issue | 7 | - |
dc.identifier.spage | 730 | - |
dc.identifier.epage | 741 | - |
dc.identifier.eissn | 2159-8290 | - |
dc.identifier.isi | WOS:000321615600021 | - |
dc.identifier.issnl | 2159-8274 | - |