Rapid detection of 2-hydroxyglutarate in frozen sections of IDH mutant tumors by MALDI-TOF mass spectrometry

Acta Neuropathologica Communications

Elena De Vita¹  Aubry K. Miller¹  Wolfgang Wick²  Stefan Pusch³  Andreas von Deimling³  Annika K. Wefers³  David E. Reuss³  Christel Herold-Mende⁴  Mark Kriegsmann⁵  Rémi Longuespée⁵  Peter Schirmacher⁵ 

[1] Cancer Drug Development, German Cancer Research Center (DKFZ);Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ);Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg;Division of Experimental Neurosurgery, Department of Neurosurgery, Heidelberg University Hospital;Institute of Pathology, Ruprecht-Karls-University Heidelberg;

关键词: IDH mutation;    2-hydroxyglutarate;    Diffuse glioma;    MALDI-TOF;    Mass spectrometry;   

DOI  :  10.1186/s40478-018-0523-3

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown