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1 H HR‐MAS and genomic analysis of human tumor biopsies discriminate between high and low grade astrocytomas
Author(s) -
Righi Valeria,
Roda Jose M.,
Paz José,
Mucci Adele,
Tugnoli Vitaliano,
RodriguezTarduchy Gemma,
Barrios Laura,
Schenetti Luisa,
Cerdán Sebastián,
GarcíaMartín María L.
Publication year - 2009
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.1377
Subject(s) - phosphocholine , choline , glioma , in vivo , downregulation and upregulation , choline kinase , in vivo magnetic resonance spectroscopy , phospholipase d , chemistry , cancer research , microbiology and biotechnology , biology , gene , enzyme , medicine , phosphatidylcholine , biochemistry , phospholipid , genetics , magnetic resonance imaging , membrane , radiology
We investigate the profile of choline metabolites and the expression of the genes of the Kennedy pathway in biopsies of human gliomas ( n = 23) using 1 H High Resolution Magic Angle Spinning (HR‐MAS, 11.7 Tesla, 277 K, 4000 Hz) and individual genetic assays. 1 H HR‐MAS spectra allowed the resolution and relative quantification by the LCModel of the resonances from choline (Cho), phosphocholine (PC) and glycerophosphorylcholine (GPC), the three main components of the combined tCho peak observed in gliomas by in vivo 1 H NMR spectroscopy. All glioma biopsies depicted a prominent tCho peak. However, the relative contributions of Cho, PC, and GPC to tCho were different for low and high grade gliomas. Whereas GPC is the main component in low grade gliomas, the high grade gliomas show a dominant contribution of PC. This circumstance allowed the discrimination of high and low grade gliomas by 1 H HR‐MAS, a result that could not be obtained using the tCho/Cr ratio commonly used by in vivo 1 H NMR spectroscopy. The expression of the genes involved in choline metabolism has been investigated in the same biopsies. High grade gliomas depict an upregulation of the β gene of choline kinase and phospholipase C, as well as a downregulation of the cytidyltransferase B gene, the balance of these being consistent with the accumulation of PC. In the low grade gliomas, phospholipase A 1 and lysophospholypase are upregulated and phospholipase D is downregulated, supporting the accumulation of GPC. The present findings offer a promising procedure that will potentially help to accurately grade glioma tumors using 1 H HR‐MAS, providing in addition the genetic background for the alterations of choline metabolism observed in high and low grade gliomas. Copyright © 2009 John Wiley & Sons, Ltd.