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Rapid detection of 2-hydroxyglutarate in frozen sections of IDH mutant tumors by MALDI-TOF mass spectrometry
- Source :
- Acta Neuropathologica Communications, Vol 6, Iss 1, Pp 1-9 (2018)
- Publication Year :
- 2018
- Publisher :
- BMC, 2018.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 20515960
- Volume :
- 6
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Acta Neuropathologica Communications
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.b7c5e40d272844c78d37c0f59ef2edce
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s40478-018-0523-3