IDENTIFYING THE ROLE OF Y-BOX BINDING PROTEIN 1 (YB1) IN HISTONE 3 MUTATED PAEDIATRIC HIGH GRADE GLIOMAS

Abstract AIMS Brain tumours are the leading cause of paediatric cancer death in the UK. Subgroup Histone 3 mutated pHGG is difficult to treat. Y-Box binding protein 1 (YB-1) is a multifunctional oncoprotein and is over-expressed in multiple different cancers. Our previous research has highlighted YB-1 as an interacting protein of mutant H3 proteins in pHGG. METHODS Localisation and expression studies of YB-1 in four cell lines, SF188 (H3 WT), KNS42 (H3G34V) and Astrocytes and HeLa as controls was performed through immunofluorescence and Western blot experiments, along with statistical analysis. YB-1 was inhibited with drugs for cell proliferation assays. RESULTS Astrocytes showed statistically significantly lower cell expression of YB-1, than pHGG cell lines. Nucleus- cytoplasmic difference in YB-1 expression was observed between different pHGG cell lines. Western blot results found, astrocytes to have the lower YB-1 expression than pHGG cells as well. Results of above studies will be presented. CONCLUSION YB-1 is significantly over-expressed in H3 mutated pHGG and has high potential as a therapeutic target for pHGG. Nuclear translocation of YB-1 is associated with H3 mutated pHHG and future investigation of Akt involvement in this process should be undertaken, along with potential association of YB-1 nuclear expression and glioma tumour grading.