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2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated glioma patients

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1, 2) have been demonstrated in the majority of World Health Organization grade 2 and grade 3 gliomas in adults. These mutations are associated with the accumulation of 2-hydroxyglutarate (2HG) within the tumor. Here we report the noninvasive detecti...

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Detalles Bibliográficos
Autores principales: Choi, Changho, Ganji, Sandeep K., DeBerardinis, Ralph J., Hatanpaa, Kimmo J., Rakheja, Dinesh, Kovacs, Zoltan, Yang, Xiao-Li, Mashimo, Tomoyuki, Raisanen, Jack M., Marin-Valencia, Isaac, Pascual, Juan M., Madden, Christopher J., Mickey, Bruce E., Malloy, Craig M., Bachoo, Robert, Maher, Elizabeth A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615719/
https://www.ncbi.nlm.nih.gov/pubmed/22281806
http://dx.doi.org/10.1038/nm.2682
Descripción
Sumario:Mutations in isocitrate dehydrogenase 1 and 2 (IDH1, 2) have been demonstrated in the majority of World Health Organization grade 2 and grade 3 gliomas in adults. These mutations are associated with the accumulation of 2-hydroxyglutarate (2HG) within the tumor. Here we report the noninvasive detection of 2HG by proton magnetic resonance spectroscopy (MRS). The pulse sequence was developed and optimized with numerical and phantom analyses for 2HG detection. The concentrations of 2HG were estimated using spectral fitting in the tumors of 30 patients. Detection of 2HG correlated with mutations in IDH1 or IDH2 and with increased levels of D-2HG by mass spectrometry of resected tumor. Noninvasive detection of 2HG may prove to be a valuable diagnostic and prognostic biomarker.