1. Intraoperative detection of isocitrate dehydrogenase mutations in human gliomas using a miniature mass spectrometer
- Author
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Mitesh V. Shah, Hannah Marie Brown, Fan Pu, Zheng Ouyang, Aaron A. Cohen-Gadol, James D. Miller, Scott Shapiro, Mahua Dey, and R. Graham Cooks
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Spectrometry, Mass, Electrospray Ionization ,Biopsy ,Mutant ,02 engineering and technology ,01 natural sciences ,Biochemistry ,Article ,Analytical Chemistry ,Cohort Studies ,Intraoperative Period ,Tandem Mass Spectrometry ,Glioma ,medicine ,Humans ,Noise level ,Brain Neoplasms ,Chemistry ,Small footprint ,010401 analytical chemistry ,Miniature mass spectrometer ,021001 nanoscience & nanotechnology ,medicine.disease ,Molecular biology ,Isocitrate Dehydrogenase ,0104 chemical sciences ,Isocitrate dehydrogenase ,Power consumption ,Mutation ,Mutation (genetic algorithm) ,0210 nano-technology - Abstract
Knowledge of the isocitrate dehydrogenase (IDH) mutation status of glioma patients could provide insights for decision-making during brain surgery. However, pathology is not able to provide such information intraoperatively. Here we describe the first application of a miniature mass spectrometer (MS) to the determination of IDH mutation status in gliomas intraoperatively. The instrumentation was modified to be compatible with use in the operating room. Tandem MS was performed on the oncometabolite, 2-hydroxyglutarate, and a reference metabolite, glutamate, which is not involved in the IDH mutation. Ratios of fragment ion intensities were measured to calculate an IDH mutation score, which was used to differentiate IDH mutant and wild-type tissues. The results of analyzing 25 biopsies from 13 patients indicate that reliable determination of IDH mutation status was achieved (p = 0.0001, using the Kruskal-Wallis non-parametric test). With its small footprint and low power consumption and noise level, this application of miniature mass spectrometers represents a simple and cost-effective platform for an important intraoperative measurement. Graphical abstract.
- Published
- 2019
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