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High resolution magic angle spinning 1H NMR of childhood brain and nervous system tumours.

Wilson M, Davies NP, Brundler MA, McConville C, Grundy RG, Peet AC - Mol. Cancer (2009)

Bottom Line: Glial tumours had significantly (two tailed t-test p < 0.05) higher creatine and glutamine and lower taurine, phosphoethanolamine, phosphorylcholine and choline compared with primitive neuro-ectodermal tumours.Classification accuracy was 90%.Medulloblastomas (n = 9) had significantly (two tailed t-test p < 0.05) higher creatine, glutamine, phosphorylcholine, glycine and scyllo-inositol than neuroblastomas (n = 7), classification accuracy was 94%.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cancer Sciences, University of Birmingham, Birmingham, UK. martin@pipegrep.co.uk

ABSTRACT

Background: Brain and nervous system tumours are the most common solid cancers in children. Molecular characterisation of these tumours is important for providing novel biomarkers of disease and identifying molecular pathways which may provide putative targets for new therapies. 1H magic angle spinning NMR spectroscopy (1H HR-MAS) is a powerful tool for determining metabolite profiles from small pieces of intact tissue and could potentially provide important molecular information.

Methods: Forty tissue samples from 29 children with glial and primitive neuro-ectodermal tumours were analysed using HR-MAS (600 MHz Varian gHX nanoprobe). Tumour spectra were fitted to a library of individual metabolite spectra to provide metabolite values. These values were then used in a two tailed t-test and multi-variate analysis employing a principal component analysis and a linear discriminant analysis. Classification accuracy was estimated using a leave-one-out analysis and B632+ bootstrapping.

Results: Glial tumours had significantly (two tailed t-test p < 0.05) higher creatine and glutamine and lower taurine, phosphoethanolamine, phosphorylcholine and choline compared with primitive neuro-ectodermal tumours. Classification accuracy was 90%. Medulloblastomas (n = 9) had significantly (two tailed t-test p < 0.05) higher creatine, glutamine, phosphorylcholine, glycine and scyllo-inositol than neuroblastomas (n = 7), classification accuracy was 94%. Supratentorial primitive neuro-ectodermal tumours had metabolite profiles in keeping with other primitive neuro-ectodermal tumours whilst ependymomas (n = 2) had metabolite profiles intermediate between pilocytic astrocytomas (n = 10) and primitive neuro-ectodermal tumours.

Conclusion: HR-MAS identified key differences in the metabolite profiles of childhood brain and nervous system improving the molecular characterisation of these tumours. Further investigation of the underlying molecular pathways is required to assess their potential as targets for new agents.

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Related in: MedlinePlus

HR-MAS spectra. High resolution magic angle spinning 1H NMR spectra for the five tumour groups studied. Spectra were baseline corrected [36] and then scaled to the spectral area between 0.5 ppm and 4.5 ppm. Tau – Taurine, PEth – phosphorylethanolamine, PC – phosphorylcholine, m-Ins – myo-inositol, Lac – lactate, Gly – glycine, GPC – glycerophosphorylcholine, Gln – glutamine, Glu – glutamate, Cr – creatine.
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Figure 6: HR-MAS spectra. High resolution magic angle spinning 1H NMR spectra for the five tumour groups studied. Spectra were baseline corrected [36] and then scaled to the spectral area between 0.5 ppm and 4.5 ppm. Tau – Taurine, PEth – phosphorylethanolamine, PC – phosphorylcholine, m-Ins – myo-inositol, Lac – lactate, Gly – glycine, GPC – glycerophosphorylcholine, Gln – glutamine, Glu – glutamate, Cr – creatine.

Mentions: Mean metabolite values for the three main tumour groups, medulloblastoma, neuroblastoma and pilocytic astrocytoma are given in Table 2. LDA was performed on the first 6 principal components from these tumour groups. From the scores plot of Figure 5, each tumour group is separable with no overlap. The classifier accuracy was 80% with an error rate of 32%. The first two discriminant functions were used to calculate scores for the ependymoma and supratentorial-PNET samples which were plotted on Figure 4. The ependymomas lie between the PNET and glial tumours whilst the supratentorial-PNET is between the neuroblastomas and the medulloblastomas. Typical spectra for the five tumour groups are shown in Figure 6.


High resolution magic angle spinning 1H NMR of childhood brain and nervous system tumours.

Wilson M, Davies NP, Brundler MA, McConville C, Grundy RG, Peet AC - Mol. Cancer (2009)

HR-MAS spectra. High resolution magic angle spinning 1H NMR spectra for the five tumour groups studied. Spectra were baseline corrected [36] and then scaled to the spectral area between 0.5 ppm and 4.5 ppm. Tau – Taurine, PEth – phosphorylethanolamine, PC – phosphorylcholine, m-Ins – myo-inositol, Lac – lactate, Gly – glycine, GPC – glycerophosphorylcholine, Gln – glutamine, Glu – glutamate, Cr – creatine.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651110&req=5

Figure 6: HR-MAS spectra. High resolution magic angle spinning 1H NMR spectra for the five tumour groups studied. Spectra were baseline corrected [36] and then scaled to the spectral area between 0.5 ppm and 4.5 ppm. Tau – Taurine, PEth – phosphorylethanolamine, PC – phosphorylcholine, m-Ins – myo-inositol, Lac – lactate, Gly – glycine, GPC – glycerophosphorylcholine, Gln – glutamine, Glu – glutamate, Cr – creatine.
Mentions: Mean metabolite values for the three main tumour groups, medulloblastoma, neuroblastoma and pilocytic astrocytoma are given in Table 2. LDA was performed on the first 6 principal components from these tumour groups. From the scores plot of Figure 5, each tumour group is separable with no overlap. The classifier accuracy was 80% with an error rate of 32%. The first two discriminant functions were used to calculate scores for the ependymoma and supratentorial-PNET samples which were plotted on Figure 4. The ependymomas lie between the PNET and glial tumours whilst the supratentorial-PNET is between the neuroblastomas and the medulloblastomas. Typical spectra for the five tumour groups are shown in Figure 6.

Bottom Line: Glial tumours had significantly (two tailed t-test p < 0.05) higher creatine and glutamine and lower taurine, phosphoethanolamine, phosphorylcholine and choline compared with primitive neuro-ectodermal tumours.Classification accuracy was 90%.Medulloblastomas (n = 9) had significantly (two tailed t-test p < 0.05) higher creatine, glutamine, phosphorylcholine, glycine and scyllo-inositol than neuroblastomas (n = 7), classification accuracy was 94%.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cancer Sciences, University of Birmingham, Birmingham, UK. martin@pipegrep.co.uk

ABSTRACT

Background: Brain and nervous system tumours are the most common solid cancers in children. Molecular characterisation of these tumours is important for providing novel biomarkers of disease and identifying molecular pathways which may provide putative targets for new therapies. 1H magic angle spinning NMR spectroscopy (1H HR-MAS) is a powerful tool for determining metabolite profiles from small pieces of intact tissue and could potentially provide important molecular information.

Methods: Forty tissue samples from 29 children with glial and primitive neuro-ectodermal tumours were analysed using HR-MAS (600 MHz Varian gHX nanoprobe). Tumour spectra were fitted to a library of individual metabolite spectra to provide metabolite values. These values were then used in a two tailed t-test and multi-variate analysis employing a principal component analysis and a linear discriminant analysis. Classification accuracy was estimated using a leave-one-out analysis and B632+ bootstrapping.

Results: Glial tumours had significantly (two tailed t-test p < 0.05) higher creatine and glutamine and lower taurine, phosphoethanolamine, phosphorylcholine and choline compared with primitive neuro-ectodermal tumours. Classification accuracy was 90%. Medulloblastomas (n = 9) had significantly (two tailed t-test p < 0.05) higher creatine, glutamine, phosphorylcholine, glycine and scyllo-inositol than neuroblastomas (n = 7), classification accuracy was 94%. Supratentorial primitive neuro-ectodermal tumours had metabolite profiles in keeping with other primitive neuro-ectodermal tumours whilst ependymomas (n = 2) had metabolite profiles intermediate between pilocytic astrocytomas (n = 10) and primitive neuro-ectodermal tumours.

Conclusion: HR-MAS identified key differences in the metabolite profiles of childhood brain and nervous system improving the molecular characterisation of these tumours. Further investigation of the underlying molecular pathways is required to assess their potential as targets for new agents.

Show MeSH
Related in: MedlinePlus