Rapid determination of isocitrate dehydrogenase mutation status of human gliomas by extraction nanoelectrospray using a miniature mass spectrometer

Anal Bioanal Chem. 2019 Mar;411(8):1503-1508. doi: 10.1007/s00216-019-01632-5. Epub 2019 Feb 2.

Abstract

Isocitrate dehydrogenase (IDH) I and II mutations in gliomas cause an abnormal accumulation of 2-hydroxyglutarate (2-HG) in these tumor cells. These mutations have potential prognostic value in that knowledge of the mutation status can lead to improved surgical resection. Information on mutation status obtained by immunohistochemistry or genomic analysis is not available during surgery. We report a rapid extraction nanoelectrospray ionization (nESI) method of determining 2-HG. This should allow the determination of IDH mutation status to be performed intraoperatively, within minutes, using a miniature mass spectrometer. This study demonstrates that the combination of tandem mass spectrometry with low-resolution mass spectrometry allows this analysis to be performed with confidence. Graphical Abstract.

Keywords: 2-Hydroxyglutarate; Clinical analysis; Glutamate; IDH mutation; Tandem mass spectrometry.

MeSH terms

  • Brain Neoplasms / genetics*
  • Equipment Design
  • Glioma / genetics*
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Mutation*
  • Paper
  • Spectrometry, Mass, Electrospray Ionization / economics
  • Spectrometry, Mass, Electrospray Ionization / instrumentation
  • Spectrometry, Mass, Electrospray Ionization / methods
  • Tandem Mass Spectrometry / economics
  • Tandem Mass Spectrometry / instrumentation*
  • Tandem Mass Spectrometry / methods
  • Time Factors

Substances

  • Isocitrate Dehydrogenase