IDH1 mutation is associated with seizures and protoplasmic subtype in patients with low-grade gliomas
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2014-01-01
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Epilepsia
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WILEY
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Medicine, Dentistry & Health Sciences
Medicine (RMH)
Surgery (RMH)
Anatomy and Neuroscience
Biomedical Engineering
Medicine (RMH)
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Anatomy and Neuroscience
Biomedical Engineering
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Liubinas, S. V., D'Abaco, G. M., Moffat, B. M., Gonzales, M., Feleppa, F., Nowell, C. J., Gorelik, A., Drummond, K. J., O'Brien, T. J., Kaye, A. H. & Morokoff, A. P. (2014). IDH1 mutation is associated with seizures and protoplasmic subtype in patients with low-grade gliomas. Epilepsia, 55 (9), pp.1438-1443. https://doi.org/10.1111/epi.12662.
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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.