¹H nuclear magnetic resonance spectroscopy characterisation of metabolic phenotypes in the medulloblastoma of the SMO transgenic mice.
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.
Hekmatyar
S K
SK
Department of Radiology, Biomedical NMR Research Center, Dartmouth College, 706 Vail, Hanover, NH 03755, USA.
Wilson
M
M
Jerome
N
N
Salek
R M
RM
Griffin
J L
JL
Peet
A
A
Kauppinen
R A
RA
D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002531:Cerebellum / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D002794:Choline / Q000032:analysis / Q000378:metabolism; D006859:Hydrogen / Q000737:chemistry; D008297:Male; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055442:Metabolome; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019906:Nuclear Magnetic Resonance, Biomolecular; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000502:physiology; D000072086:Smoothened Receptor; D013654:Taurine / Q000032:analysis / Q000378:metabolism; D047368:Tumor Burden / Q000502:physiology
D014408:Biomarkers, Tumor; D043562:Receptors, G-Protein-Coupled; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D013654:Taurine; D006859:Hydrogen; D002794:Choline