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

Francesca Branzoli, Clement Pontoizeau, Lucien Tchara, Anna Luisa Di Stefano, Aurelie Kamoun, Dinesh K Deelchand, Romain Valabrègue, Stephane Lehericy, Marc Sanson, Chris Ottolenghi, Małgorzata Marjańska

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)765-774
Number of pages10
JournalNeuro-Oncology
Volume21
Issue number6
DOIs
StatePublished - Jun 10 2019

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Cystathionine
Glioma
Magnetic Resonance Spectroscopy
Phosphoglycerate Dehydrogenase
Liquid Chromatography
Serine
Mass Spectrometry
Cystathionine gamma-Lyase
Polymerase Chain Reaction
Brain Neoplasms
Glutathione
Chromosomes
Biopsy
Gene Expression
Amino Acids

Cite this

Branzoli, F., Pontoizeau, C., Tchara, L., Di Stefano, A. L., Kamoun, A., Deelchand, D. K., ... Marjańska, M. (2019). Cystathionine as a marker for 1p/19q codeleted gliomas by in vivo magnetic resonance spectroscopy. Neuro-Oncology, 21(6), 765-774. https://doi.org/10.1093/neuonc/noz031

Cystathionine as a marker for 1p/19q codeleted gliomas by in vivo magnetic resonance spectroscopy. / Branzoli, Francesca; Pontoizeau, Clement; Tchara, Lucien; Di Stefano, Anna Luisa; Kamoun, Aurelie; Deelchand, Dinesh K; Valabrègue, Romain; Lehericy, Stephane; Sanson, Marc; Ottolenghi, Chris; Marjańska, Małgorzata.

In: Neuro-Oncology, Vol. 21, No. 6, 10.06.2019, p. 765-774.

Research output: Contribution to journalArticle

Branzoli, F, Pontoizeau, C, Tchara, L, Di Stefano, AL, Kamoun, A, Deelchand, DK, Valabrègue, R, Lehericy, S, Sanson, M, Ottolenghi, C & Marjańska, M 2019, 'Cystathionine as a marker for 1p/19q codeleted gliomas by in vivo magnetic resonance spectroscopy', Neuro-Oncology, vol. 21, no. 6, pp. 765-774. https://doi.org/10.1093/neuonc/noz031
Branzoli, Francesca ; Pontoizeau, Clement ; Tchara, Lucien ; Di Stefano, Anna Luisa ; Kamoun, Aurelie ; Deelchand, Dinesh K ; Valabrègue, Romain ; Lehericy, Stephane ; Sanson, Marc ; Ottolenghi, Chris ; Marjańska, Małgorzata. / Cystathionine as a marker for 1p/19q codeleted gliomas by in vivo magnetic resonance spectroscopy. In: Neuro-Oncology. 2019 ; Vol. 21, No. 6. pp. 765-774.
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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.",
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T1 - Cystathionine as a marker for 1p/19q codeleted gliomas by in vivo magnetic resonance spectroscopy

AU - Branzoli, Francesca

AU - Pontoizeau, Clement

AU - Tchara, Lucien

AU - Di Stefano, Anna Luisa

AU - Kamoun, Aurelie

AU - Deelchand, Dinesh K

AU - Valabrègue, Romain

AU - Lehericy, Stephane

AU - Sanson, Marc

AU - Ottolenghi, Chris

AU - Marjańska, Małgorzata

PY - 2019/6/10

Y1 - 2019/6/10

N2 - 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.

AB - 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.

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