1H MRS identifies specific metabolite profiles associated with MYCN-amplified and non-amplified tumour subtypes of neuroblastoma cell lines

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1H MRS identifies specific metabolite profiles associated with MYCN-amplified and non-amplified tumour subtypes of neuroblastoma cell lines. / Peet, Andrew; McConville, Carmel; Wilson, Martin; Levine, Baruch; Reed, M; Dyer, SA; Edwards, EC; Strachan, MC; McMullan, DJ; Wilkes, TM; Grundy, Richard.

In: NMR in biomedicine, Vol. 20, No. 7, 01.11.2007, p. 692-700.

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@article{9fafb4af8312421494bf0c291b5783ea,
title = "1H MRS identifies specific metabolite profiles associated with MYCN-amplified and non-amplified tumour subtypes of neuroblastoma cell lines",
abstract = "Neuroblastoma is the most common extracranial solid malignancy in children. The disease possesses a broad range of clinical phenotypes with widely varying prognoses. Numerous studies have sought to identify the associated genetic abnormalities in the tumour, resulting in the identification of useful prognostic markers. In particular, the presence of multiple copies of the MYCN oncogene (referred to as MYCN amplification) has been found to confer a poor prognosis. However, the molecular pathways involved are as yet poorly defined. Metabolite profiles generated by in vitro (1)H MRS provide a means of investigating the downstream metabolic consequences of genetic alterations and can identify potential targets for new agents. Thirteen neuroblastoma cell lines possessing multiple genetic alterations were investigated; seven were MYCN amplified and six MYCN non-amplified. In vitro magic angle spinning (1)H MRS was performed on cell suspensions, and the spectra analysed to obtain metabolite concentration ratios relative to total choline (tCho). A principal component analysis using these concentration ratios showed that MYCN-amplified and non-amplified cell lines form separate classes according to their metabolite profiles. Phosphocholine/tCho and taurine/tCho were found to be significantly raised (p <0.05) and glycerophosphocholine/tCho significantly reduced (p <0.05) in the MYCN-amplified compared with the MYCN non-amplified cell lines (two-tailed t test). (1)H MRS of the SH-EP1 cell line and an isogenic cell line transfected with the MYCN oncogene also showed that MYCN oncogene over-expression causes alterations in phosphocholine, glycerophosphocholine and taurine concentrations. Molecular pathways of choline and taurine metabolism are potential targets for new agents tailored to MYCN-amplified neuroblastoma. Copyright (c) 2007 John Wiley & Sons, Ltd.",
keywords = "metabolite profiles, H-1 MRS, magic angle spinning, neuroblastoma, MYCN",
author = "Andrew Peet and Carmel McConville and Martin Wilson and Baruch Levine and M Reed and SA Dyer and EC Edwards and MC Strachan and DJ McMullan and TM Wilkes and Richard Grundy",
year = "2007",
month = nov,
day = "1",
doi = "10.1002/nbm.1181",
language = "English",
volume = "20",
pages = "692--700",
journal = "NMR in biomedicine",
issn = "0952-3480",
publisher = "Wiley",
number = "7",

}

RIS

TY - JOUR

T1 - 1H MRS identifies specific metabolite profiles associated with MYCN-amplified and non-amplified tumour subtypes of neuroblastoma cell lines

AU - Peet, Andrew

AU - McConville, Carmel

AU - Wilson, Martin

AU - Levine, Baruch

AU - Reed, M

AU - Dyer, SA

AU - Edwards, EC

AU - Strachan, MC

AU - McMullan, DJ

AU - Wilkes, TM

AU - Grundy, Richard

PY - 2007/11/1

Y1 - 2007/11/1

N2 - Neuroblastoma is the most common extracranial solid malignancy in children. The disease possesses a broad range of clinical phenotypes with widely varying prognoses. Numerous studies have sought to identify the associated genetic abnormalities in the tumour, resulting in the identification of useful prognostic markers. In particular, the presence of multiple copies of the MYCN oncogene (referred to as MYCN amplification) has been found to confer a poor prognosis. However, the molecular pathways involved are as yet poorly defined. Metabolite profiles generated by in vitro (1)H MRS provide a means of investigating the downstream metabolic consequences of genetic alterations and can identify potential targets for new agents. Thirteen neuroblastoma cell lines possessing multiple genetic alterations were investigated; seven were MYCN amplified and six MYCN non-amplified. In vitro magic angle spinning (1)H MRS was performed on cell suspensions, and the spectra analysed to obtain metabolite concentration ratios relative to total choline (tCho). A principal component analysis using these concentration ratios showed that MYCN-amplified and non-amplified cell lines form separate classes according to their metabolite profiles. Phosphocholine/tCho and taurine/tCho were found to be significantly raised (p <0.05) and glycerophosphocholine/tCho significantly reduced (p <0.05) in the MYCN-amplified compared with the MYCN non-amplified cell lines (two-tailed t test). (1)H MRS of the SH-EP1 cell line and an isogenic cell line transfected with the MYCN oncogene also showed that MYCN oncogene over-expression causes alterations in phosphocholine, glycerophosphocholine and taurine concentrations. Molecular pathways of choline and taurine metabolism are potential targets for new agents tailored to MYCN-amplified neuroblastoma. Copyright (c) 2007 John Wiley & Sons, Ltd.

AB - Neuroblastoma is the most common extracranial solid malignancy in children. The disease possesses a broad range of clinical phenotypes with widely varying prognoses. Numerous studies have sought to identify the associated genetic abnormalities in the tumour, resulting in the identification of useful prognostic markers. In particular, the presence of multiple copies of the MYCN oncogene (referred to as MYCN amplification) has been found to confer a poor prognosis. However, the molecular pathways involved are as yet poorly defined. Metabolite profiles generated by in vitro (1)H MRS provide a means of investigating the downstream metabolic consequences of genetic alterations and can identify potential targets for new agents. Thirteen neuroblastoma cell lines possessing multiple genetic alterations were investigated; seven were MYCN amplified and six MYCN non-amplified. In vitro magic angle spinning (1)H MRS was performed on cell suspensions, and the spectra analysed to obtain metabolite concentration ratios relative to total choline (tCho). A principal component analysis using these concentration ratios showed that MYCN-amplified and non-amplified cell lines form separate classes according to their metabolite profiles. Phosphocholine/tCho and taurine/tCho were found to be significantly raised (p <0.05) and glycerophosphocholine/tCho significantly reduced (p <0.05) in the MYCN-amplified compared with the MYCN non-amplified cell lines (two-tailed t test). (1)H MRS of the SH-EP1 cell line and an isogenic cell line transfected with the MYCN oncogene also showed that MYCN oncogene over-expression causes alterations in phosphocholine, glycerophosphocholine and taurine concentrations. Molecular pathways of choline and taurine metabolism are potential targets for new agents tailored to MYCN-amplified neuroblastoma. Copyright (c) 2007 John Wiley & Sons, Ltd.

KW - metabolite profiles

KW - H-1 MRS

KW - magic angle spinning

KW - neuroblastoma

KW - MYCN

U2 - 10.1002/nbm.1181

DO - 10.1002/nbm.1181

M3 - Article

C2 - 17506115

VL - 20

SP - 692

EP - 700

JO - NMR in biomedicine

JF - NMR in biomedicine

SN - 0952-3480

IS - 7

ER -