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¹H nuclear magnetic resonance spectroscopy characterisation of metabolic phenotypes in the medulloblastoma of the SMO transgenic mice.

Title: ¹H nuclear magnetic resonance spectroscopy characterisation of metabolic phenotypes in the medulloblastoma of the SMO transgenic mice.
Authors: Hekmatyar, SK
Wilson, M
Jerome, N
Salek, RM
Griffin, JL
Peet, A
Kauppinen, RA
Item Type: Journal Article
Abstract: BACKGROUND: Human medulloblastomas exhibit diverse molecular pathology. Aberrant hedgehog signalling is found in 20-30% of human medulloblastomas with largely unknown metabolic consequences. METHODS: Transgenic mice over-expressing smoothened (SMO) receptor in granule cell precursors with high incidence of exophytic medulloblastomas were sequentially followed up by magnetic resonance imaging (MRI) and characterised for metabolite phenotypes by ¹H MR spectroscopy (MRS) in vivo and ex vivo using high-resolution magic angle spinning (HR-MAS) ¹H MRS. RESULTS: Medulloblastomas in the SMO mice presented as T₂ hyperintense tumours in MRI. These tumours showed low concentrations of N-acetyl aspartate and high concentrations of choline-containing metabolites (CCMs), glycine, and taurine relative to the cerebellar parenchyma in the wild-type (WT) C57BL/6 mice. In contrast, ¹H MRS metabolite concentrations in normal appearing cerebellum of the SMO mice were not different from those in the WT mice. Macromolecule and lipid ¹H MRS signals in SMO medulloblastomas were not different from those detected in the cerebellum of WT mice. The HR-MAS analysis of SMO medulloblastomas confirmed the in vivo ¹H MRS metabolite profiles, and additionally revealed that phosphocholine was strongly elevated in medulloblastomas accounting for the high in vivo CCM. CONCLUSIONS: These metabolite profiles closely mirror those reported from human medulloblastomas confirming that SMO mice provide a realistic model for investigating metabolic aspects of this disease. Taurine, glycine, and CCM are potential metabolite biomarkers for the SMO medulloblastomas. The MRS data from the medulloblastomas with defined molecular pathology is discussed in the light of metabolite profiles reported from human tumours.
Issue Date: 12-Oct-2010
Date of Acceptance: 12-Aug-2010
URI: http://hdl.handle.net/10044/1/82200
DOI: 10.1038/sj.bjc.6605890
ISSN: 0007-0920
Publisher: Springer Nature [academic journals on nature.com]
Start Page: 1297
End Page: 1304
Journal / Book Title: British Journal of Cancer
Volume: 103
Issue: 8
Copyright Statement: © 2010 Cancer Research UK All rights reserved. From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
Keywords: Animals
Biomarkers, Tumor
Cerebellar Neoplasms
Cerebellum
Choline
Hydrogen
Male
Medulloblastoma
Metabolome
Mice
Mice, Inbred C57BL
Mice, Transgenic
Nuclear Magnetic Resonance, Biomolecular
Phenotype
Receptors, G-Protein-Coupled
Smoothened Receptor
Taurine
Tumor Burden
Cerebellum
Animals
Mice, Inbred C57BL
Mice, Transgenic
Mice
Medulloblastoma
Cerebellar Neoplasms
Hydrogen
Choline
Taurine
Receptors, G-Protein-Coupled
Tumor Burden
Nuclear Magnetic Resonance, Biomolecular
Phenotype
Male
Metabolome
Biomarkers, Tumor
Smoothened Receptor
Animals
Biomarkers, Tumor
Cerebellar Neoplasms
Cerebellum
Choline
Hydrogen
Male
Medulloblastoma
Metabolome
Mice
Mice, Inbred C57BL
Mice, Transgenic
Nuclear Magnetic Resonance, Biomolecular
Phenotype
Receptors, G-Protein-Coupled
Smoothened Receptor
Taurine
Tumor Burden
Oncology & Carcinogenesis
1112 Oncology and Carcinogenesis
1117 Public Health and Health Services
Publication Status: Published
Conference Place: England
Online Publication Date: 2010-09-14
Appears in Collections:Department of Metabolism, Digestion and Reproduction



This item is licensed under a Creative Commons License Creative Commons