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Isocitrate dehydrogenase mutations in gliomas.

Publication ,  Journal Article
Waitkus, MS; Diplas, BH; Yan, H
Published in: Neuro Oncol
January 2016

Over the last decade, extraordinary progress has been made in elucidating the underlying genetic causes of gliomas. In 2008, our understanding of glioma genetics was revolutionized when mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) were identified in the vast majority of progressive gliomas and secondary glioblastomas (GBMs). IDH enzymes normally catalyze the decarboxylation of isocitrate to generate α-ketoglutarate (αKG), but recurrent mutations at Arg(132) of IDH1 and Arg(172) of IDH2 confer a neomorphic enzyme activity that catalyzes reduction of αKG into the putative oncometabolite D-2-hydroxyglutate (D2HG). D2HG inhibits αKG-dependent dioxygenases and is thought to create a cellular state permissive to malignant transformation by altering cellular epigenetics and blocking normal differentiation processes. Herein, we discuss the relevant literature on mechanistic studies of IDH1/2 mutations in gliomas, and we review the potential impact of IDH1/2 mutations on molecular classification and glioma therapy.

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Published In

Neuro Oncol

DOI

EISSN

1523-5866

Publication Date

January 2016

Volume

18

Issue

1

Start / End Page

16 / 26

Location

England

Related Subject Headings

  • Oncology & Carcinogenesis
  • Mutation
  • Ketoglutaric Acids
  • Isocitrate Dehydrogenase
  • Humans
  • Glutarates
  • Glioma
  • Glioblastoma
  • Brain Neoplasms
  • Animals
 

Citation

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Waitkus, M. S., Diplas, B. H., & Yan, H. (2016). Isocitrate dehydrogenase mutations in gliomas. Neuro Oncol, 18(1), 16–26. https://doi.org/10.1093/neuonc/nov136
Waitkus, Matthew S., Bill H. Diplas, and Hai Yan. “Isocitrate dehydrogenase mutations in gliomas.Neuro Oncol 18, no. 1 (January 2016): 16–26. https://doi.org/10.1093/neuonc/nov136.
Waitkus MS, Diplas BH, Yan H. Isocitrate dehydrogenase mutations in gliomas. Neuro Oncol. 2016 Jan;18(1):16–26.
Waitkus, Matthew S., et al. “Isocitrate dehydrogenase mutations in gliomas.Neuro Oncol, vol. 18, no. 1, Jan. 2016, pp. 16–26. Pubmed, doi:10.1093/neuonc/nov136.
Waitkus MS, Diplas BH, Yan H. Isocitrate dehydrogenase mutations in gliomas. Neuro Oncol. 2016 Jan;18(1):16–26.
Journal cover image

Published In

Neuro Oncol

DOI

EISSN

1523-5866

Publication Date

January 2016

Volume

18

Issue

1

Start / End Page

16 / 26

Location

England

Related Subject Headings

  • Oncology & Carcinogenesis
  • Mutation
  • Ketoglutaric Acids
  • Isocitrate Dehydrogenase
  • Humans
  • Glutarates
  • Glioma
  • Glioblastoma
  • Brain Neoplasms
  • Animals