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1H HR-MAS and genomic analysis of human tumor biopsies discriminate between high and low grade astrocytomas

AuthorsRighi, Valeria; Roda, José M.; Rodríguez-Tarduchy, Gemma ; Barrios, Laura; Cerdán, Sebastián ; García-Martín, María L.
Issue Date2009
CitationNMR in Biomedicine 22(6): 629-637 (2009)
AbstractWe investigate the profile of choline metabolites and the expression of the genes of the Kennedy pathway in biopsies of human gliomas (n=23) using 1H High Resolution Magic Angle Spinning (HR-MAS, 11.7 Tesla, 277 K, 4000 Hz) and individual genetic assays. 1H 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 1H 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 1H HR-MAS, a result that could not be obtained using the tCho/Cr ratio commonly used by in vivo 1H 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 A1 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 1H HR-MAS, providing in addition the genetic background for the alterations of choline metabolism observed in high and low grade gliomas.
Identifiersdoi: 10.1002/nbm.1377
issn: 0952-3480
e-issn: 1099-1492
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