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IDH mutation analysis in gliomas as a diagnostic and prognostic biomarker

Research output: Contribution to journalArticle

  • K M Kurian
  • Harry R Haynes
  • C Crosby
  • K Hopkins
  • M Williams
Original languageEnglish
JournalBritish Journal of Neurosurgery
DOIs
DatePublished - 1 Mar 2013

Abstract

Introduction. There is a high rate of IDH1/2 mutations in low grade gliomas and in high grade gliomas deriving from them. IDH analysis of gliomas is a novel method of classification and an independent prognostic marker. We compared antibody and sequencing methods for the detection of IDH mutations. Method. 88 samples from 74 patients were identified. For immunohistochemistry: sections were stained with anti-IDH1R132H antibody. For sequencing: DNA was extracted from fresh, frozen tissue. Results. 28% (20/71) of cases were positive for the R132H IDH1 mutation by antibody. An IDH1 mutation was detected by molecular genetics in 37% (21/57) of cases and no IDH2 mutations were detected. 24% (5/21) had rare IDH1 mutations not detected by immunohistochemistry. Where sufficient tissue was available, immunohistochemistry and DNA analysis were fully concordant for the p.Arg132His mutation. Both Grade II gliomas and anaplastic astrocytomas showed a statistically different distribution of IDH1 mutation load compared to GBMs (p <0.0001; p = 0.0021 respectively). Conclusion. A rationalised combined approach involving R132H antibody testing and sequencing of negative cases would be ideal for the detection of IDH1 mutations - antibody testing is cheaper than sequencing but sequencing demonstrates rare IDH1 mutations not detected by immunohistochemistry.

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