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

F Branzoli, C Pontoizeau, L Tchara… - Neuro …, 2019 - academic.oup.com
F Branzoli, C Pontoizeau, L Tchara, AL Di Stefano, A Kamoun, DK Deelchand…
Neuro-oncology, 2019academic.oup.com
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 …
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.
Oxford University Press