We investigate the profile of choline metabolites and the expression of the genes of the Kennedy pathway in biopsies ofhuman gliomas (n¼23) using 1H High Resolution Magic Angle Spinning (HR-MAS, 11.7 Tesla, 277 K, 4000Hz) and individual genetic assays. 1H HR-MAS spectra allowed the resolution and relative quantification by the LCModel of the resonances fromcholine (Cho),phosphocholine (PC) and glycerophosphorylcholine (GPC), the three main components ofthe combined tCho peak observed in gliomas by in vivo 1H NMR spectroscopy. All glioma biopsies depicted a prominenttChopeak. However, the relative contributions ofCho, PC, andGPC totChowere different for lowandhighgrade 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 usedby in vivo 1HNMR spectroscopy. The expression of the genes involved in choline metabolismhas been investigated in the same biopsies. High grade gliomasdepict an upregulation of the beta gene of choline kinase and phospholipase C, aswell 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 thatwill potentially helptoaccuratelygrade gliomatumors using1HHR-MAS, providinginaddition the genetic background for the alterations of choline metabolism observed in high and low grade gliomas.

1H HR-MAS and genomic analysis of human tumor biopsies discriminates between high and low grade astrocytomas / V., Righi; J. M., Roda; J., Paz; Mucci, Adele; V., Tugnoli; G., Rodriguez Tarduchy; L., Barrios; Schenetti, Luisa; S., Cerdán; M. L., García Martín. - In: NMR IN BIOMEDICINE. - ISSN 0952-3480. - STAMPA. - 22:6(2009), pp. 629-637. [10.1002/nbm.1377]

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

MUCCI, Adele;SCHENETTI, Luisa;
2009

Abstract

We investigate the profile of choline metabolites and the expression of the genes of the Kennedy pathway in biopsies ofhuman gliomas (n¼23) using 1H High Resolution Magic Angle Spinning (HR-MAS, 11.7 Tesla, 277 K, 4000Hz) and individual genetic assays. 1H HR-MAS spectra allowed the resolution and relative quantification by the LCModel of the resonances fromcholine (Cho),phosphocholine (PC) and glycerophosphorylcholine (GPC), the three main components ofthe combined tCho peak observed in gliomas by in vivo 1H NMR spectroscopy. All glioma biopsies depicted a prominenttChopeak. However, the relative contributions ofCho, PC, andGPC totChowere different for lowandhighgrade 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 usedby in vivo 1HNMR spectroscopy. The expression of the genes involved in choline metabolismhas been investigated in the same biopsies. High grade gliomasdepict an upregulation of the beta gene of choline kinase and phospholipase C, aswell 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 thatwill potentially helptoaccuratelygrade gliomatumors using1HHR-MAS, providinginaddition the genetic background for the alterations of choline metabolism observed in high and low grade gliomas.
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1H HR-MAS and genomic analysis of human tumor biopsies discriminates between high and low grade astrocytomas / V., Righi; J. M., Roda; J., Paz; Mucci, Adele; V., Tugnoli; G., Rodriguez Tarduchy; L., Barrios; Schenetti, Luisa; S., Cerdán; M. L., García Martín. - In: NMR IN BIOMEDICINE. - ISSN 0952-3480. - STAMPA. - 22:6(2009), pp. 629-637. [10.1002/nbm.1377]
V., Righi; J. M., Roda; J., Paz; Mucci, Adele; V., Tugnoli; G., Rodriguez Tarduchy; L., Barrios; Schenetti, Luisa; S., Cerdán; M. L., García Martín
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/615635
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