Detection of IDH1 and IDH2 mutations by fluorescence melting curve analysis as a diagnostic tool for brain biopsies

Craig Horbinski, Lindsey Kelly, Yuri E. Nikiforov, Mary Beth Durso, Marina N. Nikiforova

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Novel mutations in the isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) genes have been identified in a large proportion of diffuse gliomas. Tumors with IDH1/2 mutations have distinctive clinical characteristics, including a less aggressive course. The aim of this study was to develop and evaluate the performance of a novel real-time PCR and post-PCR fluorescence melting curve analysis assay for the detection of IDH1 and IDH2 mutations in routine formalinfixed, paraffin-embedded tissues of brain biopsies. Using the established assay, we tested 67 glial neoplasms, 57 non-neoplastic conditions that can often mimic gliomas (eg, radiation changes, viral infections, infarctions, etc), and 44 noncentral nervous system tumors. IDH1 and IDH2 mutations were detected in 72% of lower grade diffuse gliomas and in 17% of glioblastomas. The IDH1 mutation was the most common (93%), with the most frequent subtype being R132H (88%). These mutations were not identified in non-neoplastic glioma mimickers and in noncentral nervous system tumors including thyroid carcinomas. The results of this assay had a 100% correlation with the results obtained by conventional sequencing. In summary, we report here the real-time PCR/fluorescence melting curve analysis assay that provides rapid and sensitive detection of IDH mutations in formalin-fixed, paraffinembedded tissues, and is therefore useful as a powerful adjunct diagnostic tool for refining histopathological diagnosis of brain lesions and guiding patient management.

Original languageEnglish (US)
Pages (from-to)487-492
Number of pages6
JournalJournal of Molecular Diagnostics
Volume12
Issue number4
DOIs
StatePublished - Jul 1 2010

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Medicine

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