MBRS-20. KETOLYTIC AND GLYCOLYTIC ENZYMATIC EXPRESSION IN PAEDIATRIC MEDULLOBLASTOMAS: IMPLICATION FOR KETOGENIC DIET THERAPY. Issue 2 (22nd June 2018)

• Record Type: Journal Article
• Authors: Storer, Lisa C D; de Beer, Zacharias; Lockwood, George; Paine, Simon; Grundy, Richard G
• Is Part Of: Neuro-oncology. Volume 20:Issue 2(2018)supplement 2
• Page Start: i132
• Page End: i132
• Publication Date: 2018-06-22
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy059.465
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Medulloblastomas are the most common malignant brain tumour of childhood. Long term survival is approximately 75%, however, therapy often results in disabling outcomes and reduced quality of survival. One potential strategy to improve outcome, whilst reducing side effects, is exploiting the metabolic differences between normal and tumour cells. Under normal physiological conditions, brain cells metabolise glucose for energy. If "starved" of glucose, ketone bodies are metabolised. Mitochondrial defects in brain tumour cells obviate this metabolic flexibility resulting in glycolytic dependence. Thus, a high fat, low carbohydrate ketogenic diet (KD) may control tumour growth. We evaluated the expression of succinyl-CoA:3-oxoacid CoA transferase 1 (OXCT1) and D-β-hydroxybutyrate dehydrogenase 1 (BDH1), both involved in ketone body utilization and pyruvate kinase M2 (PKM2), essential for aerobic glycolysis, in 84 paediatric medulloblastomas by immunohistochemistry. Expression was assessed as low (<20%) or high (>20%). 70.2% showed low expression of OXCT1 and 82.5% of BDH1. Low expression of either results in an inability to metabolise ketones. 34.9% showed high expression of PKM2, increasing the Warburg effect and when combined with low expression of BDH1 (27.5%) or OXCT1 (22.0%), the optimal immunohistochemistry profile, to arrest ketone metabolism. No statistical difference was seen with gender or age. Expression of OXCT1 was significantly lower in children with a Group 4 medulloblastoma (p=0.032) when compared to other molecular subgroups (WNT, SHH and Group 3). Therefore the KD may offer a potential addition to current medulloblastoma therapies including in the prevention of disseminated recurrence characteristic of Group 4 tumours.