Rapid and sensitive intraoperative detection of mutations in the isocitrate dehydrogenase 1 and 2 genes during surgery for glioma: Laboratory investigation

Masayuki Kanamori, Atsuo Kikuchi, Mika Watanabe, Ichiyo Shibahara, Ryuta Saito, Yoji Yamashita, Yukihiko Sonoda, Toshihiro Kumabe, Shigeo Kure, Teiji Tominaga

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Object. Intraoperative diagnosis is important in determining the strategies during surgery for glioma. Because the mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes have diagnostic, prognostic, and predictive values, the authors assessed the feasibility and significance of a simplified method for the intraoperative detection of IDH1 and IDH2 gene mutations. Methods. Rapid DNA extraction, amplification with conventional polymerase chain reaction (PCR) or co-amplification at lower denaturation temperature PCR (COLD-PCR), and fluorescence melting curve analysis with adjacent hybridization probes were performed for the intraoperative detection of IDH1 and IDH2 mutations in 18 cases of suspected nonneoplastic lesions and low- and high-grade gliomas and in 3 cases of radiation necrosis. Results. DNA extraction for detection of the mutation took 60-65 minutes. The results of this assay showed complete correlation with that of Sanger sequencing. The sensitivity for detection of mutations in a background of wild-type genes was 12.5% and 2.5% in conventional PCR and COLD-PCR, respectively. The diagnosis of glioma was established in 3 of 5 cases in which definitive diagnosis was not obtained using frozen sections, and information was obtained for the discrimination of glioblastoma or glioblastoma with an oligodendroglioma component from anaplastic glioma or secondary glioblastoma. This assay also detected a small fraction of tumor cells with IDH1 mutation in radiation necrosis. Conclusions. These methods provide important information for establishing the differential diagnosis between low-grade glioma and nonneoplastic lesions and the diagnosis for subtypes of high-grade glioma. Although tumor cells in radiation necrosis were detected with a high sensitivity, further investigation is necessary for clinical application in surgery for recurrent glioma.

Original languageEnglish
Pages (from-to)1288-1297
Number of pages10
JournalJournal of neurosurgery
Volume120
Issue number6
DOIs
Publication statusPublished - 2014 Jun

Keywords

  • Glioma
  • IDH1
  • IDH2
  • Intraoperative molecular diagnosis
  • Oncology

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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