Investigating notch1 pathway components in histone 3.3 mutant paediatric high-grade glioma

Abstract AIMS High-grade gliomas (HGG) in adults and children (paediatric high-grade glioma, pHGG) differ in molecular characteristics, despite having the same morphological features. Although pHGG has a low incidence, it contributes to 40% of all brain tumour death in childhood. Histone 3 (H3) mutation is a unique feature of pHGG. The understanding the pathophysiology of these tumour are important to develop more targeted therapy for these tumours. Our previous research has identified, increased activation of the Notch1 pathway in H3 mutated tumours. We have now explored the relationship between the Notch1 pathway components to H3 mutated pHGG. We hypothesised that The Notch1 pathway components (NICD1, HES1, HES5) are dysregulated in the Histone 3 mutant tumours in comparison to H3 wild type tumours. METHOD Protein expression analyses, immunofluorescence and microscopy and western blot experiments were per- formed, to assess the localization and expression of Notch1 pathway components (NICD1, HES1, HES5), using cultures H3.3 wildtype and H3.3 mutant cell lines. RESULTS The results show that Notch1 pathway expression differ between H3 mutant and H3 wild type tumours. CONCLUSIONS These results suggest that components of Notch1 pathway (HES1/HES5) are dysregulated, which may be driving tumour growth in this H3 mutated tumour. Therefore, we can explore Notch1 Pathway components as targeted therapeutic options.