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Intraoperative detection of isocitrate dehydrogenase mutations in human gliomas using a miniature mass spectrometer

Analytical and Bioanalytical Chemistry volume 411, pages 7929–7933 (2019)Cite this article

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.

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Acknowledgments

The authors thank clinical research nurses Lauren Snyder and Heather Cero at Goodman Campbell Brain and Spin (Indianapolis, IN) for patient consent, providing clinical data, and IRB monitoring; Clint Alfaro and Tsdale Mehari for assistance in sample preparation; Robert Schrader for assistance with instrumentation; Zhuoer Xie for the table of contents figure; and PURSPEC Technologies Inc. for instrumentation support.

Funding

This study received funding from the Purdue University Center for Cancer Research Small Grants Program; from National Institute of General Medical Sciences of the NIH under award number R44GM119584.

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Author notes

  1. Hannah Marie Brown and Fan Pu contributed equally to this work.

Affiliations

  1. Department of Chemistry and Bindley Biosciences Center, Purdue University, 560 Oval Drive, West Lafayette, IN, 47907-1393, USA

    Hannah Marie Brown, Fan Pu, Zheng Ouyang & R. Graham Cooks

  2. Department of Neurological Surgery, Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Mahua Dey, James Miller, Mitesh V. Shah, Scott A. Shapiro & Aaron A. Cohen-Gadol

  3. Department of Precision Instrument, Tsinghua University, Beijing, 100084, China

    Zheng Ouyang

Authors
  1. Hannah Marie Brown
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  2. Fan Pu
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  3. Mahua Dey
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  4. James Miller
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  6. Scott A. Shapiro
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  7. Zheng Ouyang
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  8. Aaron A. Cohen-Gadol
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  9. R. Graham Cooks
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Corresponding author

Correspondence to R. Graham Cooks.

Ethics declarations

Biopsies for tissue analysis were obtained from human subjects undergoing tumor resection for suspected glioma at IU Health Methodist Hospital, after they had provided written informed consent to participate in the research study, following an IUSM IRB approved protocol (IRB No. 1410342262). No results were shared with the neurosurgeons during the surgical resection so as not to affect the standard of care.

Conflict of interest

Zheng Ouyang is the founder of PURSPEC Technologies Inc. All other authors declare that they have no conflict of interest.

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Brown, H.M., Pu, F., Dey, M. et al. Intraoperative detection of isocitrate dehydrogenase mutations in human gliomas using a miniature mass spectrometer. Anal Bioanal Chem 411, 7929–7933 (2019). https://doi.org/10.1007/s00216-019-02198-y

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  • DOI: https://doi.org/10.1007/s00216-019-02198-y

Keywords

  • Molecular cancer diagnostics
  • Ambient ionization mass spectrometry
  • Isocitrate dehydrogenase mutation
  • Miniature mass spectrometry
  • Point-of-care diagnostics