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Absolute Quantification of 2-Hydroxyglutarate on Tissue by MALDI MSI for Rapid and Precise Identification of IDH Mutations in Human Glioma.

Isocitrate dehydrogenase (IDH) gene mutations are important predictive molecular markers to guide surgical strategy in brain cancer therapy. Herein, we presented a method using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) for absolute quantification of 2-hydroxyglutarate (2-HG) on tissues to identify IDH mutations and evaluate tumour residue. This analytical method was tested among 34 glioma patients and validated with gold standard clinical technologies. The cut-off value of 2-HG was set as 0.81 pmol/μg to identify IDH mutant (IDHmt) gliomas with 100% specificity and sensitivity. In addition, 2-HG levels and tumour cell density (TCD) showed positive correlation in IDHmt gliomas by this spatial method. This MALDI MSI-based absolute quantification method has great potentiality for incorporating into surgical workflow in the future. This article is protected by copyright. All rights reserved.