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Rapid detection of mutation in isocitrate dehydrogenase 1 and 2 genes using mass spectrometry

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Abstract

The 2016 World Health Organization classification of tumors of the central nervous system was recently revised. Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes and chromosome 1p/19q codeletion are especially important for both the integrated diagnosis and the determination of surgical strategy. To establish a method for intraoperative molecular diagnosis, a simple, rapid method was developed for the measurement of 2-hydroxyglutarate (2-HG), a specific oncometabolite formed in the presence of IDH gene mutation, using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI–MS/MS). This method requires only 10 min to measure the level of 2-HG from tissue preparation to completion of examination. Using this method, the level of 2-HG was analyzed in 105 patients with diffuse infiltrating glioma, and showed that IDH mutated glioma had significantly higher level of 2-HG compared to IDH wild-type glioma. Receiver operating characteristic curve analysis showed the area under the curve, sensitivity, and specificity were 0.9815, 97.5, and 100%, respectively. In contrast, tumor grade and presence of chromosome 1p/19q codeletion in the IDH mutated glioma could not be predicted from the level of 2-HG. Measurement of 2-HG level using LC/ESI–MS/MS can provide rapid and accurate information of mutation status in the IDH gene.

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Abbreviations

AUC:

Area under the curve

2-HG:

2-Hydroxyglutarate

IDH:

Isocitrate dehydrogenase

IS:

Internal standard

LC/ESI–MS/MS:

Liquid chromatography/electrospray ionization tandem mass spectrometry

LC–MS/MS:

Liquid chromatography tandem mass spectrometry

ROC:

Receiver operating characteristic

SRM:

Selected reaction monitoring

WHO:

World Health Organization

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Acknowledgements

This work was supported by Grants-in-Aid for Scientific Research (no. 16K10749) from the Japan Society for the Promotion of Science.

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Correspondence to Masayuki Kanamori.

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Kanamori, M., Maekawa, M., Shibahara, I. et al. Rapid detection of mutation in isocitrate dehydrogenase 1 and 2 genes using mass spectrometry. Brain Tumor Pathol 35, 90–96 (2018). https://doi.org/10.1007/s10014-018-0317-0

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  • DOI: https://doi.org/10.1007/s10014-018-0317-0

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