In: Acta Neuropathologica Communications, 6 (2018), Nr. 21. pp. 1-9. ISSN 2051-5960

Preview

PDF, English Download (1MB) | Lizenz: Rapid detection of 2-hydroxyglutarate in frozen sections of IDH mutant tumors by MALDI-TOF mass spectrometry by Longuespée, Rémi ; Wefers, Annika K. ; De Vita, Elena ; Miller, Aubry K. ; Reuss, David E. ; Wick, Wolfgang ; Herold-Mende, Christel ; Kriegsmann, Mark ; Schirmacher, Peter ; von Deimling, Andreas ; Pusch, Stefan underlies the terms of Creative Commons Attribution 4.0

Abstract

All isocitrate dehydrogenase (IDH) mutant solid neoplasms exhibit highly elevated levels of D-2-hydroxyglutarate (D-2HG). Detection of 2HG in tumor tissues currently is performed by gas or liquid chromatography-mass spectrometry (GC- or LC-MS) or biochemical detection. While these methods are highly accurate, a considerable amount of time for tissue preparation and a relatively high amount of tissue is required for testing. We here present a rapid approach to detect 2HG in brain tumor tissue based on matrix-assisted laser desorption ionization - time of flight mass spectrometry (MALDI-TOF). We analyzed 26 brain tumor samples with known IDH1 or IDH2 mutation and compared readouts to those from 28 brain tumor samples of wildtype IDH status. IDH mutant samples exhibited a clear positive signal for 2HG which was not observed in any of the IDH wildtype tumors. Our analytical pipeline allowed for 2HG detection in less than 5 min. Data were validated by determining 2HG levels in all tissues with a biochemical assay. In conclusion, we developed a protocol for rapid detection of 2HG levels and illustrate the possibility to use MALDI-TOF for the detection of metabolites on frozen tissue sections in a diagnostic setting.