Integrated proteogenomic analysis of medulloblastoma progression (WGS)

Medulloblastoma is a malignant pediatric brain cancer, whose primary tumors are representatively classified into four molecular subgroups, WNT, SHH, Group 3 and 4. Although the molecular characters have been known well, conventional chemotherapy and radiotherapy after surgery have been used for the treatment to young children, which cause harmful side effects to their chronic health conditions. Moreover, the patients frequently suffer from recurrence and have shown poor prognosis following relapse. Here, we characterized the five layers of molecular profiles and identified potential therapeutic targets of medulloblastoma by performing multi-omics-based analysis including mass spectrometric proteome analysis. The proteome-added integrated analyses characterized new subtypes which showed specific protein functions, such as cell cycle (SHHa), EMT (G4a) and neuronal (G4b and SHHb) functions. Based on the kinase-substrate relations of phospho-proteome, we found the kinase-centered functional modularity of each subtype. These features were significantly associated with clinical features, such as recurrence and progression, and informed us the therapeutic options. Thus, we suggest that our data and analysis would support molecular basis and clinically applicable targets for precision diagnostics and therapeutics of medulloblastoma.