Combination of high-resolution magic angle spinning proton magnetic resonance spectroscopy and microscale genomics to type brain tumor biopsies (Journal article)

Tzika, A. A./ Astrakas, L./ Cao, H. H./ Mintzopoulos, D./ Andronesi, O. C./ Mindrinos, M./ Zhang, J. W./ Rahme, L. G./ Blekas, K./ Likas, A. C./ Galatsanos, N. P./ Carroll, R. S./ Black, P. M.

Advancements in the diagnosis and prognosis of brain tumor patients, and thus in their survival and quality of life, can be achieved using biomarkers that facilitate improved tumor typing. We introduce and implement a combinatorial metabolic and molecular approach that applies state-of-the-art, high-resolution magic angle spinning (HRMAS) proton (H-1) MRS and gene transcriptome profiling to intact brain tumor biopsies, to identify unique biomarker profiles of brain tumors. Our results show that samples as small as 2 mg can be successfully processed, the HRMAS H-1 MRS procedure does not result in mRNA degradation, and minute mRNA amounts yield high-quality genomic data. The MRS and genomic analyses demonstrate that CNS tumors have altered levels of specific H-1 MRS metabolites that directly correspond to altered expression of Kennedy pathway genes; and exhibit rapid phospholipid turnover, which coincides with upregulation of cell proliferation genes. The data also suggest Sonic Hedgehog pathway (SHH) dysregulation may play a role in anaplastic ganglioglioma pathogenesis. That a strong correlation is seen between the HRMAS H-1 MRS and genomic data cross-validates and further demonstrates the biological relevance of the MRS results. Our combined metabolic/molecular MRS/genomic approach provides insights into the biology of anaplastic ganglioglioma and a new potential tumor typing methodology that could aid neurologists and neurosurgeons to improve the diagnosis, treatment, and ongoing evaluation of brain tumor patients.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Μηχανικών Ηλεκτρονικών Υπολογιστών και Πληροφορικής
Keywords: brain/cns cancers,tumor biomarkers,anaplastic ganglioglioma,ex vivo high-resolution magic angle spinning magnetic resonance spectroscopy,genomics,choline phospholipid-metabolism,mammary epithelial-cells,in-vivo,nmr-spectroscopy,gene-expression,imaging biomarkers,kinase inhibitors,breast-cancer,spectra,quantification
ISSN: 1107-3756
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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