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Isocitrate dehydrogenase mutations in gliomas: mechanisms, biomarkers and therapeutic target.

Publication ,  Journal Article
Guo, C; Pirozzi, CJ; Lopez, GY; Yan, H
Published in: Curr Opin Neurol
December 2011

PURPOSE OF REVIEW: Isocitrate dehydrogenases, IDH1 and IDH2, decarboxylate isocitrate to α-ketoglutarate (α-KG) and reduce NADP to NADPH. Point mutations of IDH1 and IDH2 have been discovered in gliomas. IDH mutations cause loss of native enzymatic activities and confer novel activity of converting α-KG to 2-hydroxyglutarate (2-HG). The mechanisms of IDH mutations in gliomagenesis, and their value as diagnostic, prognostic marker and therapeutic target have been extensively studied. This review is to summarize the findings of these studies. RECENT FINDINGS: Crystal structural studies revealed conformation changes in mutant IDHs, which may explain the gain of function by mutant IDHs. The product of mutant IDHs, 2-HG, is an inhibitor of α-KG-dependent dioxygenases, which may cause genome-wide epigenetic changes in human gliomas. IDH mutations are a favorable prognostic factor for human glioma and can be used as biomarker for differential diagnosis and subclassification rather than predictor of response to treatment. Preliminary data suggested that inhibiting production of the substrate of mutant IDH enzymes caused slow-down of glioma cell growth. SUMMARY: As valuable diagnostic and prognostic markers of human gliomas, there is still a lack of knowledge on biological functions of mutant IDHs, making targeting IDHs in glioma both difficult and unsecured.

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Published In

Curr Opin Neurol

DOI

EISSN

1473-6551

Publication Date

December 2011

Volume

24

Issue

6

Start / End Page

648 / 652

Location

England

Related Subject Headings

  • Protein Conformation
  • Prognosis
  • Point Mutation
  • Neurology & Neurosurgery
  • Ketoglutaric Acids
  • Isoenzymes
  • Isocitrates
  • Isocitrate Dehydrogenase
  • Humans
  • Glioma
 

Citation

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Guo, C., Pirozzi, C. J., Lopez, G. Y., & Yan, H. (2011). Isocitrate dehydrogenase mutations in gliomas: mechanisms, biomarkers and therapeutic target. Curr Opin Neurol, 24(6), 648–652. https://doi.org/10.1097/WCO.0b013e32834cd415
Guo, Changcun, Christopher J. Pirozzi, Giselle Y. Lopez, and Hai Yan. “Isocitrate dehydrogenase mutations in gliomas: mechanisms, biomarkers and therapeutic target.Curr Opin Neurol 24, no. 6 (December 2011): 648–52. https://doi.org/10.1097/WCO.0b013e32834cd415.
Guo C, Pirozzi CJ, Lopez GY, Yan H. Isocitrate dehydrogenase mutations in gliomas: mechanisms, biomarkers and therapeutic target. Curr Opin Neurol. 2011 Dec;24(6):648–52.
Guo, Changcun, et al. “Isocitrate dehydrogenase mutations in gliomas: mechanisms, biomarkers and therapeutic target.Curr Opin Neurol, vol. 24, no. 6, Dec. 2011, pp. 648–52. Pubmed, doi:10.1097/WCO.0b013e32834cd415.
Guo C, Pirozzi CJ, Lopez GY, Yan H. Isocitrate dehydrogenase mutations in gliomas: mechanisms, biomarkers and therapeutic target. Curr Opin Neurol. 2011 Dec;24(6):648–652.

Published In

Curr Opin Neurol

DOI

EISSN

1473-6551

Publication Date

December 2011

Volume

24

Issue

6

Start / End Page

648 / 652

Location

England

Related Subject Headings

  • Protein Conformation
  • Prognosis
  • Point Mutation
  • Neurology & Neurosurgery
  • Ketoglutaric Acids
  • Isoenzymes
  • Isocitrates
  • Isocitrate Dehydrogenase
  • Humans
  • Glioma