IDH1 mutation is associated with seizures and protoplasmic subtype in patients with low-grade gliomas

Simon V. Liubinas, Giovanna M. D'Abaco, Bradford Moffat, Michael Gonzales, Frank Feleppa, Cameron Nowell, Alexandra Gorelik, Katharine J. Drummond, Terence J. O'Brien, Andrew H. Kaye, Andrew P. Morokoff

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47 Citations (Scopus)

Abstract

Objective: The isocitrate dehydrogenase 1 (IDH1) R132H mutation is the most common mutation in World Health Organization (WHO) grade II gliomas, reported to be expressed in 70-80%, but only 5-10% of high grade gliomas. Low grade tumors, especially the protoplasmic subtype, have the highest incidence of tumor associated epilepsy (TAE). The IDH1 mutation leads to the accumulation of 2-hydroxyglutarate (2HG), a metabolite that bears a close structural similarity to glutamate, an excitatory neurotransmitter that has been implicated in the pathogenesis of TAE. We hypothesized that expression of mutated IDH1 may play a role in the pathogenesis of TAE in low grade gliomas.

Methods: Thirty consecutive patients with WHO grade II gliomas were analyzed for the presence of the IDH1-R132H mutation using immunohistochemistry. The expression of IDH1 mutation was semiquantified using open-source biologic-imaging analysis software.

Results: The percentage of cells positive for the IDH1-R132H mutation was found to be higher in patients with TAE compared to those without TAE (median and interquartile range (IQR) 25.3% [8.6-53.5] vs. 5.2% [0.6-13.4], p = 0.03). In addition, we found a significantly higher median IDH1 mutation expression level in the protoplasmic subtype of low grade glioma (52.2% [IQR 19.9-58.6] vs. 13.8% [IQR 3.9-29.4], p = 0.04).

Significance: Increased expression of the IDH1-R132H mutation is associated with seizures in low grade gliomas and also with the protoplasmic subtype. This supports the hypothesis that this mutation may play a role in the pathogenesis of both TAE and low grade gliomas.

Original languageEnglish
Pages (from-to)1438-1443
Number of pages6
JournalEpilepsia
Volume55
Issue number9
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • Epilepsy
  • Glioma
  • Glutamate
  • IDH1
  • Protoplasmic astrocytoma
  • Seizure

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