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

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.

• Authors: Rémi Longuespée, Annika K Wefers, Elena De Vita, Aubry K Miller, David E Reuss, Wolfgang Wick, Christel Herold-Mende, Mark Kriegsmann, Peter Schirmacher, Andreas von Deimling, Stefan Pusch
• Journal: Acta neuropathologica communications (Acta Neuropathol Commun) Vol. 6 Issue 1 Pg. 21 (03 02 2018) ISSN: 2051-5960 [Electronic] England
• PMID: 29499756 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study)

Chemical References

• Biomarkers, Tumor
• Glutarates
• alpha-hydroxyglutarate
• IDH2 protein, human
• Isocitrate Dehydrogenase
• IDH1 protein, human

Topics

• Biomarkers, Tumor (analysis, genetics, metabolism)
• Brain (metabolism, pathology)
• Brain Chemistry
• Brain Neoplasms (chemistry, genetics, metabolism, pathology)
• Cryopreservation
• Glioma (chemistry, genetics, metabolism, pathology)
• Glutarates (analysis, metabolism)
• Humans
• Immunohistochemistry
• Isocitrate Dehydrogenase (genetics)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization (methods)
• Time Factors