Identification of novel therapeutic targets for histone 3 mutated children’s brain tumour, using unique tumour cell surface proteomic signatures

Abstract Aims Improvements in the treatments for childhood and adolescent brain tumours, High-Grade Glioma (pHGG) Diffuse Intrinsic Pontine Glioblastoma (DIPG), have not advanced much they continue to carry a very poor prognosis. These tumours are now defined by mutations affecting histone 3 proteins, indeed 80% of DIPGs harbour H3.1 H3.3 K27M somatic whilst 30% pHGGs exhibit G34R or G34V mutations. We hypothesized that mutant will distinct mutation specific surfactome (cell membrane proteins) signature. Method therefore analysed cell surface proteomics pHGG DIPG, order identify novel targets therapy. at first isolated fractions from range patient cells carrying different (G34R, G34V), relative wild type 3. A comparative quantitative mass-spectrometry analyses these is then performed. Results The results obtained date demonstrated unique differential expression patterns which correlated type. For example, increased Ras-related proteins Rab-3, Rab-3D detected only H3.3-G34R mutated line comparison. Conclusion Identification proteins’ association with pHGG, help precise therapeutic targets, benefiting patients receive therapy based on tumour’s molecular