Biological significance of mutant isocitrate dehydrogenase 1 and 2 in gliomagenesis

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

Mutations of the isocitrate dehydrogenase (IDH) genes are considered an important event that occurs at an early stage during gliomagenesis. The mutations often occur in grade 2 or 3 gliomas and secondary glioblastomas. Most IDH mutations are associated with codon 132 and 172 in IDH1 and IDH2 in gliomas, respectively. While IDH1 and IDH2 catalyze the oxidative decarboxylation of isocitrate to form α-ketoglutarate (α-KG), IDH1 and IDH2 mutations convert α-KG to 2-hydroxyglutarate (2-HG). The accumulation of oncometabolite 2-HG is believed to lead progenitor cells into gliomas, inhibiting several α-KG-dependent enzymes, including ten-eleven translocation enzymes, histone demethylases, and prolyl hydroxylases, although the mechanisms have not been fully revealed. Herein, we review the contribution of IDH1 and IDH2 mutations to gliomagenesis.

Original languageEnglish
Pages (from-to)170-179
Number of pages10
JournalNeurologia medico-chirurgica
Volume56
Issue number4
DOIs
Publication statusPublished - 15-04-2016

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Isocitrate Dehydrogenase
Mutation
Glioma
Histone Demethylases
Prolyl Hydroxylases
Decarboxylation
Enzymes
Glioblastoma
Codon
Stem Cells
Genes

All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology

Cite this

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abstract = "Mutations of the isocitrate dehydrogenase (IDH) genes are considered an important event that occurs at an early stage during gliomagenesis. The mutations often occur in grade 2 or 3 gliomas and secondary glioblastomas. Most IDH mutations are associated with codon 132 and 172 in IDH1 and IDH2 in gliomas, respectively. While IDH1 and IDH2 catalyze the oxidative decarboxylation of isocitrate to form α-ketoglutarate (α-KG), IDH1 and IDH2 mutations convert α-KG to 2-hydroxyglutarate (2-HG). The accumulation of oncometabolite 2-HG is believed to lead progenitor cells into gliomas, inhibiting several α-KG-dependent enzymes, including ten-eleven translocation enzymes, histone demethylases, and prolyl hydroxylases, although the mechanisms have not been fully revealed. Herein, we review the contribution of IDH1 and IDH2 mutations to gliomagenesis.",
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Biological significance of mutant isocitrate dehydrogenase 1 and 2 in gliomagenesis. / Ohba, Shigeo; Hirose, Yuichi.

In: Neurologia medico-chirurgica, Vol. 56, No. 4, 15.04.2016, p. 170-179.

Research output: Contribution to journalReview article

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AB - Mutations of the isocitrate dehydrogenase (IDH) genes are considered an important event that occurs at an early stage during gliomagenesis. The mutations often occur in grade 2 or 3 gliomas and secondary glioblastomas. Most IDH mutations are associated with codon 132 and 172 in IDH1 and IDH2 in gliomas, respectively. While IDH1 and IDH2 catalyze the oxidative decarboxylation of isocitrate to form α-ketoglutarate (α-KG), IDH1 and IDH2 mutations convert α-KG to 2-hydroxyglutarate (2-HG). The accumulation of oncometabolite 2-HG is believed to lead progenitor cells into gliomas, inhibiting several α-KG-dependent enzymes, including ten-eleven translocation enzymes, histone demethylases, and prolyl hydroxylases, although the mechanisms have not been fully revealed. Herein, we review the contribution of IDH1 and IDH2 mutations to gliomagenesis.

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