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Metabolite Profile Differences in Childhood Brain Tumors: 1H Magic Angle Spinning NMR Spectroscopy

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Pediatric Cancer, Volume 2

Part of the book series: Pediatric Cancer ((PECA,volume 2))

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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 High Resolution Magic Angle Spinning NMR spectroscopy (HR-MAS) is an emerging technique for determining metabolite profiles from small pieces of intact tissue and whole cells grown in culture, making it ideal for molecular characterisation of disease.

Method: 22 tissue samples from children with brain tumours and 7 cell lines originating from medulloblastoma (2), neuroblastoma (2), supertentorial PNET (1) and retinoblastoma (2) were analysed using HR-MAS. Spectra were fitted to a library of individual metabolite spectra to provide metabolite values, Principle Component Analysis (PCA) was used to investigate the metabolic relationship between the tumour types.

Results: Primitive neuroectodermal and glial based tumours were linearly separable using PCA, demonstrating that histological features of the tissue were closely related to their metabolite profiles. Each cultured cell line was found to have a distinct metabolite profile. The desmoplastic and classic variants of medulloblastoma were particularly distinct, with large differences in the distribution of choline containing metabolites.

Conclusion: HR-MAS identified key differences in the metabolite profiles of childhood brain tumour tissue and cells grown in culture, improving the molecular characterisation of these tumours and showing the promise of HR-MAS as a rapid diagnostic aid. Further investigation of the underlying molecular pathways is required to assess their potential as targets for new agents.

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References

  • Badiali M, Pession A, Basso G, Andreini L, Rigobello L, Galassi E, Giangaspero F (1991) N-myc and c-myc oncogenes amplification in medulloblastomas. Evidence of particularly aggressive behavior of a tumor with c-myc amplification. Tumori 77(2):118–121

    PubMed  CAS  Google Scholar 

  • Barton SJ, Howe FA, Tomlins AM, Cudlip SA, Nicholson JK, Bell BA, Griffiths JR (1999) Comparison of in vivo 1H MRS of human brain tumours with 1H HR-MAS spectroscopy of intact biopsy samples in vitro. MAGMA 8(2):121–128

    Article  PubMed  CAS  Google Scholar 

  • Borel M, Degoul F, Communal Y, Mounetou E, Bouchon B, C-Gaudreault R, Madelmont JC, Miot-Noirault E (2007) N-(4-iodophenyl)-N′-(2-chloroethyl)urea as a microtubule disrupter: in vitro and in vivo profiling of antitumoral activity on CT-26 murine colon carcinoma cell line cultured and grafted to mice. Br J Cancer 96(11):1684–1691

    Article  PubMed  CAS  Google Scholar 

  • Chang Q, Chen Z, You J, McNutt MA, Zhang T, Han Z, Zhang X, Gong E, Gu J (2007) All-trans-retinoic acid induces cell growth arrest in a human medulloblastoma cell line. J Neurooncol 84(3):263–267

    Article  PubMed  CAS  Google Scholar 

  • Cheng LL, Ma MJ, Becerra L, Ptak T, Tracey I, Lackner A, González RG (1997) Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy. Proc Natl Acad Sci USA 94(12):6408–6413

    Article  PubMed  CAS  Google Scholar 

  • Davies NP, Wilson M, Harris LM, Natarajan K, Lateef S, MacPherson L, Sgouros S, Grundy RG, Arvanitis TN, Peet AC (2008) Identification and characterisation of childhood cerebellar tumours by in vivo proton MRS. NMR Biomed 21(8):908–918

    Article  PubMed  CAS  Google Scholar 

  • Davies NP, Wilson M, Natarajan K, Sun Y, MacPherson L, Brundler M, Arvanitis TN, Grundy RG, Peet AC (2010) Non-invasive detection of glycine as a biomarker of malignancy in childhood brain tumours using in-vivo 1H MRS at 1.5 Tesla confirmed by ex-vivo high-resolution magic-angle spinning NMR. NMR Biomed 23(1):80–87

    Article  PubMed  CAS  Google Scholar 

  • Easton JM, Harris LM, Viant MR, Peet AC, Arvanitis TN (2010) Linked metabolites: a tool for the construction of directed metabolic graphs. Comput Biol Med 40(3):340–349

    Article  PubMed  CAS  Google Scholar 

  • Griffin JL, Shockcor JP (2004) Metabolic profiles of cancer cells. Nat Rev Cancer 4(7):551–561

    Article  PubMed  CAS  Google Scholar 

  • Griffin JL, Mann CJ, Scott J, Shoulders CC, Nicholson JK (2001) Choline containing metabolites during cell transfection: an insight into magnetic resonance spectroscopy detectable changes. FEBS Lett 509(2):263–266

    Article  PubMed  CAS  Google Scholar 

  • Griffin JL, Bollard M, Nicholson JK, Bhakoo K (2002) Spectral profiles of cultured neuronal and glial cells derived from HRMAS (1)H NMR spectroscopy. NMR Biomed 15(6):375–384

    Article  PubMed  CAS  Google Scholar 

  • Kinoshita Y, Kajiwara H, Yokota A, Koga Y (1993) Proton magnetic resonance spectroscopy of astrocytic tumors: an in vitro study. Neurol Med Chir (Tokyo) 33(6):350–359

    Article  CAS  Google Scholar 

  • Lehnhardt F, Bock C, Röhn G, Ernestus R, Hoehn M (2005) Metabolic differences between primary and recurrent human brain tumors: a 1H NMR spectroscopic investigation. NMR Biomed 18(6):371–382

    Article  PubMed  CAS  Google Scholar 

  • Lyng H, Sitter B, Bathen TF, Jensen LR, Sundfør K, Kristensen GB, Gribbestad IS (2007) Metabolic mapping by use of high-resolution magic angle spinning 1H MR spectroscopy for assessment of apoptosis in cervical carcinomas. BMC Cancer 7:11

    Article  PubMed  Google Scholar 

  • Maris JM, Hogarty MD, Bagatell R, Cohn SL (2007) Neuroblastoma. Lancet 369(9579):2106–2120

    Article  PubMed  CAS  Google Scholar 

  • Martínez-Bisbal MC, Martí-Bonmatí L, Piquer J, Revert A, Ferrer P, Llácer JL, Piotto M, Assemat O, Celda B (2004) 1H and 13C HR-MAS spectroscopy of intact biopsy samples ex vivo and in vivo 1H MRS study of human high grade gliomas. NMR Biomed 17(4):191–205

    Article  PubMed  Google Scholar 

  • Martínez-Granados B, Monleón D, Martínez-Bisbal MC, Rodrigo JM, del Olmo J, Lluch P, Ferrández A, Martí-Bonmatí L, Celda B (2006) Metabolite identification in human liver needle biopsies by high-resolution magic angle spinning 1H NMR spectroscopy. NMR Biomed 19(1):90–100

    Article  PubMed  Google Scholar 

  • Moreno-Torres A, et al. (2004) Taurine detection by proton magnetic resonance spectroscopy in medulloblastoma: contribution to noninvasive differential diagnosis with cerebellar astrocytoma. Neurosurgery. 55(4):824–829, discussion 829

    Google Scholar 

  • Morvan D, Demidem A, Papon J, Madelmont JC (2003) Quantitative HRMAS proton total correlation spectroscopy applied to cultured melanoma cells treated by chloroethyl nitrosourea: demonstration of phospholipid metabolism alterations. Magn Reson Med 49(2):241–248

    Article  PubMed  CAS  Google Scholar 

  • Opstad KS, Bell BA, Griffiths JR, Howe FA (2009) Taurine: a potential marker of apoptosis in gliomas. Br J Cancer 100(5):789–794

    Article  PubMed  CAS  Google Scholar 

  • Peeling J, Sutherland G (1992) High-resolution 1H NMR spectroscopy studies of extracts of human cerebral neoplasms. Magn Reson Med 24(1):123–136

    Article  PubMed  CAS  Google Scholar 

  • Peet AC, McConville C, Wilson M, Levine BA, Reed M, Dyer SA, Edwards EC, Strachan MC, McMullan DJ, Wilkes TM, Grundy RG (2007) 1H MRS identifies specific metabolite profiles associated with MYCN-amplified and non-amplified tumour subtypes of neuroblastoma cell lines. NMR Biomed 20(7):692–700

    Article  PubMed  CAS  Google Scholar 

  • Pizzo PA, Poplack DG (2010) Principles and practice of pediatric oncology, 6th edn. Lippincott Williams and Wilkins, Philadelphia

    Google Scholar 

  • Podo F (1999) Tumour phospholipid metabolism. NMR Biomed 12(7):413–439

    Article  PubMed  CAS  Google Scholar 

  • Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME, Kim JYH, Goumnerova LC, Black PM, Lau C, Allen JC, Zagzag D, Olson JM, Curran T, Wetmore C, Biegel JA, Poggio T, Mukherjee S, Rifkin R, Califano A, Stolovitzky G, Louis DN, Mesirov JP, Lander ES, Golub TR (2002) Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 415(6870):436–442

    Article  PubMed  CAS  Google Scholar 

  • Preul MC, Caramanos Z, Collins DL, Villemure J, Leblanc R, Olivier A, Pokrupa R, Arnold DL (1996) Accurate, noninvasive diagnosis of human brain tumors by using proton magnetic resonance spectroscopy. Nat Med 2(3):323–325

    Article  PubMed  CAS  Google Scholar 

  • Rabeson H, Fauvelle F, Testylier G, Foquin A, Carpentier P, Dorandeu F, van Ormondt D, Graveron-Demilly D (2008) Quantitation with QUEST of brain HRMAS-NMR signals: application to metabolic disorders in experimental epileptic seizures. Magn Reson Med 59(6):1266–1273

    Article  PubMed  CAS  Google Scholar 

  • Reynolds CP, Matthay KK, Villablanca JG, Maurer BJ (2003) Retinoid therapy of high-risk neuroblastoma. Cancer Lett 197(1–2):185–192

    Article  PubMed  CAS  Google Scholar 

  • Reynolds G, Wilson M, Peet A, Arvanitis TN (2006) An algorithm for the automated quantitation of metabolites in in vitro NMR signals. Magn Reson Med 56(6):1211–1219

    Article  PubMed  CAS  Google Scholar 

  • R Development Core Team (2008). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0, http://www.R-project.org

  • Righi V, Andronesi OC, Mintzopoulos D, Black PM, Tzika AA (2010) High-resolution magic angle spinning magnetic resonance spectroscopy detects glycine as a biomarker in brain tumors. Int J Oncol 36(2):301–306

    PubMed  CAS  Google Scholar 

  • Sitter B, Sonnewald U, Spraul M, Fjösne HE, Gribbestad IS (2002) High-resolution magic angle spinning MRS of breast cancer tissue. NMR Biomed 15(5):327–337

    Article  PubMed  CAS  Google Scholar 

  • Sitter B, Lundgren S, Bathen TF, Halgunset J, Fjosne HE, Gribbestad IS (2006) Comparison of HR MAS MR spectroscopic profiles of breast cancer tissue with clinical parameters. NMR Biomed 19(1):30–40

    Article  PubMed  CAS  Google Scholar 

  • Sjøbakk TE, Johansen R, Bathen TF, Sonnewald U, Juul R, Torp SH, Lundgren S, Gribbestad IS (2008) Characterization of brain metastases using high-resolution magic angle spinning MRS. NMR Biomed 21(2):175–185

    Article  PubMed  Google Scholar 

  • Stearns D, Chaudhry A, Abel TW, Burger PC, Dang CV, Eberhart CG (2006) c-myc overexpression causes anaplasia in medulloblastoma. Cancer Res 66(2):673–681

    Article  PubMed  CAS  Google Scholar 

  • Sutton LN, Wehrli SL, Gennarelli L, Wang Z, Zimmerman R, Bonner K, Rorke LB (1994) High-resolution 1H-magnetic resonance spectroscopy of pediatric posterior fossa tumors in vitro. J Neurosurg 81(3):443–448

    Article  PubMed  CAS  Google Scholar 

  • Tugnoli V, Schenetti L, Mucci A, Nocetti L, Toraci C, Mavilla L, Basso G, Rovati R, Tavani F, Zunarelli E, Righi V, Tosi MR (2005) A comparison between in vivo and ex vivo HR-MAS 1H MR spectra of a pediatric posterior fossa lesion. Int J Mol Med 16(2):301–307

    PubMed  CAS  Google Scholar 

  • Tzika AA, Cheng LL, Goumnerova L, Madsen JR, Zurakowski D, Astrakas LG, Zarifi MK, Scott RM, Anthony DC, Gonzalez RG, Black PM (2002) Biochemical characterization of pediatric brain tumors by using in vivo and ex vivo magnetic resonance spectroscopy. J Neurosurg 96(6):1023–1031

    Article  PubMed  CAS  Google Scholar 

  • Tzika AA, Astrakas L, Cao H, Mintzopoulos D, Andronesi OC, Mindrinos M, Zhang J, Rahme LG, Blekas KD, Likas AC, Galatsanos NP, Carroll RS, Black PM (2007) Combination of high-resolution magic angle spinning proton magnetic resonance spectroscopy and microscale genomics to type brain tumor biopsies. Int J Mol Med 20(2):199–208

    PubMed  CAS  Google Scholar 

  • Usenius JP, Vainio P, Hernesniemi J, Kauppinen RA (1994) Choline-containing compounds in human astrocytomas studied by 1H NMR spectroscopy in vivo and in vitro. J Neurochem 63(4):1538–1543

    Article  PubMed  CAS  Google Scholar 

  • Wharton BA, Morley R, Isaacs EB, Cole TJ, Lucas A (2004) Low plasma taurine and later neurodevelopment. Arch Dis Child Fetal Neonatal Ed 89(6):F497–F498

    Article  PubMed  CAS  Google Scholar 

  • Wilson M, Davies NP, Grundy RG, Peet AC (2009) A quantitative comparison of metabolite signals as detected by in vivo MRS with ex vivo 1H HR-MAS for childhood brain tumours. NMR Biomed 22(2):213–219

    Article  PubMed  CAS  Google Scholar 

  • Wright A, Fellows G, Griffiths J, Wilson M, Bell B, Howe F (2010) Ex vivo HRMAS of adult brain tumours: metabolite quantification and assignment of tumour biomarkers. Mol Cancer 9(1)

    Google Scholar 

  • Yang Y, Li C, Nie X, Feng X, Chen W, Yue Y, Tang H, Deng F (2007) Metabonomic studies of human hepatocellular carcinoma using high-resolution magic-angle spinning 1H NMR spectroscopy in conjunction with multivariate data analysis. J Proteome Res 6(7):2605–2614

    Article  PubMed  CAS  Google Scholar 

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Wilson, M., Peet, A. (2012). Metabolite Profile Differences in Childhood Brain Tumors: 1H Magic Angle Spinning NMR Spectroscopy. In: Hayat, M. (eds) Pediatric Cancer, Volume 2. Pediatric Cancer, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2957-5_11

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