Altered cancer cell metabolism in gliomas with mutant IDH1 or IDH2.

Alexandra Borodovsky, Meghan J. Seltzer, Gregory J Riggins

Research output: Contribution to journalReview article

Abstract

IDH1/2 mutations occur in up to 70% of low-grade gliomas and secondary glioblastomas. Mutation of these enzymes reduces the wildtype function of the enzyme (conversion of isocitrate to α-ketoglutarate) while conferring a new enzymatic function, the production of D-2-hydroxyglutarate (D-2-HG) from α-ketoglutarate (α-KG). However, it is unclear how these enzymatic changes contribute to tumorigenesis. Here, we discuss the recent studies that demonstrate how IDH1/2 mutation may alter the metabolism and epigenome of gliomas, how these changes may contribute to tumor formation, and opportunities they might provide for molecular targeting. Metabolomic studies of IDH1/2 mutant cells have revealed alterations in glutamine, fatty acid, and citrate synthesis pathways. Additionally, D-2-HG produced by IDH1/2 mutant cells can competitively inhibit α-KG-dependent enzymes, including histone demethylases and DNA hydroxylases, potentially leading to a distinct epigenetic phenotype. Alterations in metabolism and DNA methylation present possible mechanisms of tumorigenesis. Recent attempts to improve outcomes for glioma patients have resulted in incremental gains. Studies of IDH1/2 mutations have provided mechanistic insights into tumorigenesis and potential avenues for therapeutic intervention. Further study of IDH1/2 mutations might allow for improved therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)83-89
Number of pages7
JournalCurrent Opinion in Oncology
Volume24
Issue number1
StatePublished - 2012
Externally publishedYes

Fingerprint

Glioma
Mutation
Carcinogenesis
Neoplasms
Enzymes
Histone Demethylases
Metabolomics
DNA Methylation
Glioblastoma
Mixed Function Oxygenases
Glutamine
Epigenomics
Citric Acid
Fatty Acids
Phenotype
DNA
Therapeutics
alpha-hydroxyglutarate

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Altered cancer cell metabolism in gliomas with mutant IDH1 or IDH2. / Borodovsky, Alexandra; Seltzer, Meghan J.; Riggins, Gregory J.

In: Current Opinion in Oncology, Vol. 24, No. 1, 2012, p. 83-89.

Research output: Contribution to journalReview article

Borodovsky, Alexandra ; Seltzer, Meghan J. ; Riggins, Gregory J. / Altered cancer cell metabolism in gliomas with mutant IDH1 or IDH2. In: Current Opinion in Oncology. 2012 ; Vol. 24, No. 1. pp. 83-89.
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