TBIO-14. Characterisation of the arginine pathway enzymes in paediatric brain tumours to determine susceptibility to therapeutic arginine depletion

Bishop, Eleanor; Dimitrova, Monika; Storer, Lisa; Grundy, Richard; Dandapani, Madhumita

Abstract

INTRODUCTION
Extracellular arginine dependency (auxotrophy) is increasingly being recognised in several tumours. This is due to the inability of cancer cells to recycle or synthesise intracellular arginine through the urea cycle pathway compared to normal cells. Whilst adult glioblastoma is known to exhibit this, the expression of the arginine pathway enzymes has not been delineated in paediatric brain tumours.
METHODS
We used immunohistochemical methods to stain for arginine pathway enzymes in Paediatric High grade glioma (pHGG), low grade glioma (pLGG) and medulloblastoma (MB) tumour tissue microarrays (TMAs). The antibodies detected protein expression of the metaboliser Arginase (Arg2), recycling enzymes ornithine transcarbamoylase (OTC), Arginosuccinate synthetase (ASS1) and arginosuccinate lyase (ASL) as well as the transporter SLC7A1.
RESULTS
Deficiency of OTC, ASS1 and ASL were seen in 92%, 98% and 93% of pHGG samples (n=156) respectively, with deficiency defined as low (

Citation

Bishop, E., Dimitrova, M., Storer, L., Grundy, R., & Dandapani, M. TBIO-14. Characterisation of the arginine pathway enzymes in paediatric brain tumours to determine susceptibility to therapeutic arginine depletion

• Presentation Conference Type: Conference Abstract
• Acceptance Date: Dec 1, 2020
• Online Publication Date: Dec 4, 2020
• Publication Date: 2020-12
• Deposit Date: Mar 19, 2021
• Publicly Available Date: Apr 19, 2021
• Journal: Neuro-Oncology
• Print ISSN: 1522-8517
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 22
• Issue: Issue Supplement_3
• Pages: iii469
• DOI: https://doi.org/10.1093/neuonc/noaa222.841
• Public URL: https://nottingham-repository.worktribe.com/output/5402694
• Publisher URL: https://academic.oup.com/neuro-oncology/article/22/Supplement_3/iii469/6019187