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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

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

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. More... »

PAGES

21

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s40478-018-0523-3

DOI

http://dx.doi.org/10.1186/s40478-018-0523-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1101319643

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29499756


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