PO15: DECREASED EXPRESSION OF THE MITOCHONDRIAL BCAT PROTEIN CORRELATES WITH IMPROVED PATIENT SURVIVAL IN IDH WILD-TYPE GLIOMAS

INTRODUCTION: Recent studies indicated that the human cytosolic branched chain aminotransferase protein (hBCATc), which metabolises the branched chain amino acids (BCAA), was significantly upregulated in IDH1/2 wild type (WT) glioblastomas and is associated with a worse prognosis compared with IDH mutant gliomas. The diagnostic and prognostic significance of markers of BCAA metabolism is currently under investigation. METHOD: 64 glioma tumour samples were compared for hBCATc, hBCATm and BCKDC expression using western blotting and IHC. DNA was extracted from fresh frozen tissue. Sanger sequencing of the p.Arg132 region of IDH1 and p.Arg172 region of IDH2 was undertaken. RESULTS: In IDH WT tumours, like hBCATc (p = 0.007), the mitochondrial isoform (hBCATm) is significantly (p = 0.036) expressed relative to IDH mutant gliomas. hBCATm additionally shows a more significant correlation with patient survival than hBCATc. In IDH WT tumours, low hBCATm expression is a positive prognostic factor (p = 0.003). hBCATm expression also correlated with WHO grade. Although previous reports indicate that increased hBCATc occurs exclusively in IDH-WT tumours, our studies demonstrate that 30% of IDH mutant tumours express hBCATc. Although hBCATc alone has been suggested as a putative therapeutic target, it is important to evaluate the expression of hBCATm as its expression may impact the efficacy of new treatments targeting hBCATc. CONCLUSION: IDH WT high grade gliomas traditionally have a poor prognosis. However we demonstrate for the first time that relatively low hBCATm may select for a better performing clinical cohort and may be a possible candidate target for drug therapy.