Cystathionine as a marker for 1p/19q codeleted gliomas by in vivo magnetic resonance spectroscopy - Sorbonne Université Access content directly
Journal Articles Neuro-Oncology Year : 2019

Cystathionine as a marker for 1p/19q codeleted gliomas by in vivo magnetic resonance spectroscopy

Abstract

Background: Codeletion of chromosome arms 1p and 19q (1p/19q codeletion) highly benefits diagnosis and prognosis in gliomas. In this study, we investigated the effect of 1p/19q codeletion on cancer cell metabolism and evaluated possible metabolic targets for tailored therapies. Methods: We combined in vivo 1H (proton) magnetic resonance spectroscopy (MRS) measurements in human gliomas with the analysis of a series of standard amino acids by liquid chromatography-mass spectroscopy (LC-MS) in human glioma biopsies. Sixty-five subjects with low-grade glioma were included in the study: 31 underwent the MRI/MRS examination, 47 brain tumor tissue samples were analyzed with LC-MS, and 33 samples were analyzed for gene expression with quantitative PCR. Additionally, we performed metabolic tracer experiments in cell models with 1p deletion. Results: We report the first in vivo detection of cystathionine by MRS in 1p/19q codeleted gliomas. Selective accumulation of cystathionine was observed in codeleted gliomas in vivo, in brain tissue samples, as well as in cells harboring heterozygous deletions for serine- and cystathionine-pathway genes located on 1p: phosphoglycerate dehydrogenase (PHGDH) and cystathionine gamma-lyase (CTH). Quantitative PCR analyses showed 40-50% lower expression of both PHGDH and CTH in 1p/19q codeleted gliomas compared with their non-codeleted counterparts. Conclusions: Our results provide strong evidence of a selective vulnerability of codeleted gliomas to serine and glutathione depletion and point to cystathionine as a possible noninvasive marker of treatment response.

Dates and versions

hal-04555677 , version 1 (23-04-2024)

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Francesca Branzoli, Clément Pontoizeau, Lucien Tchara, Anna Luisa Di Stefano, Aurélie Kamoun, et al.. Cystathionine as a marker for 1p/19q codeleted gliomas by in vivo magnetic resonance spectroscopy. Neuro-Oncology, 2019, 21 (6), pp.765-774. ⟨10.1093/neuonc/noz031⟩. ⟨hal-04555677⟩
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