Comprehensive Metabolomic Analysis of IDH1R132H Clinical Glioma Samples Reveals Suppression of β-oxidation Due to Carnitine Deficiency View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-07-05

AUTHORS

Satsuki Miyata, Kaoru Tominaga, Eiji Sakashita, Masashi Urabe, Yoshiyuki Onuki, Akira Gomi, Takashi Yamaguchi, Makiko Mieno, Hiroaki Mizukami, Akihiro Kume, Keiya Ozawa, Eiju Watanabe, Kensuke Kawai, Hitoshi Endo

ABSTRACT

Gliomas with Isocitrate dehydrogenase 1 (IDH1) mutation have alterations in several enzyme activities, resulting in various metabolic changes. The aim of this study was to determine a mechanism for the better prognosis of gliomas with IDH mutation by performing metabolomic analysis. To understand the metabolic state of human gliomas, we analyzed clinical samples obtained from surgical resection of glioma patients (grades II–IV) with or without the IDH1 mutation, and compared the results with U87 glioblastoma cells overexpressing IDH1 or IDH1R132H. In clinical samples of gliomas with IDH1 mutation, levels of D-2-hydroxyglutarate (D-2HG) were increased significantly compared with gliomas without IDH mutation. Gliomas with IDH mutation also showed decreased intermediates in the tricarboxylic acid cycle and pathways involved in the production of energy, amino acids, and nucleic acids. The marked difference in the metabolic profile in IDH mutant clinical glioma samples compared with that of mutant IDH expressing cells includes a decrease in β-oxidation due to acyl-carnitine and carnitine deficiencies. These metabolic changes may explain the lower cell division rate observed in IDH mutant gliomas and may provide a better prognosis in IDH mutant gliomas. More... »

PAGES

9787

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-019-46217-5

DOI

http://dx.doi.org/10.1038/s41598-019-46217-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1117797722

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/31278288


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34 schema:description Gliomas with Isocitrate dehydrogenase 1 (IDH1) mutation have alterations in several enzyme activities, resulting in various metabolic changes. The aim of this study was to determine a mechanism for the better prognosis of gliomas with IDH mutation by performing metabolomic analysis. To understand the metabolic state of human gliomas, we analyzed clinical samples obtained from surgical resection of glioma patients (grades II–IV) with or without the IDH1 mutation, and compared the results with U87 glioblastoma cells overexpressing IDH1 or IDH1R132H. In clinical samples of gliomas with IDH1 mutation, levels of D-2-hydroxyglutarate (D-2HG) were increased significantly compared with gliomas without IDH mutation. Gliomas with IDH mutation also showed decreased intermediates in the tricarboxylic acid cycle and pathways involved in the production of energy, amino acids, and nucleic acids. The marked difference in the metabolic profile in IDH mutant clinical glioma samples compared with that of mutant IDH expressing cells includes a decrease in β-oxidation due to acyl-carnitine and carnitine deficiencies. These metabolic changes may explain the lower cell division rate observed in IDH mutant gliomas and may provide a better prognosis in IDH mutant gliomas.
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