Proteomic analysis of human Medulloblastoma reveals distinct activated pathways between subgroups

Deregulations in fundamental signaling pathways are key events in pathogenesis of cancer. One intriguing illustration that still holds blind spots is the pediatric brain tumor arising from the developing cerebellum: medulloblastoma (MB). Extensive high-throughput sequencing led to the characterization of four MB subgroups (WNT, SHH, Group 3 and Group 4) delineated with distinct molecular signatures and clinical outcomes. However, up-to-date these analyses have not attained the global comprehension of their dynamic network complexity. Wishing to uncover a comprehensive view of all MB subgroups we employed a proteomic analysis to integrate accurate protein expression and activity that should ultimately give rise to a realistic picture of how MB cancer cells are regulated. In this study we present the first analysis regrouping methylation status, whole-transcriptome sequencing and quantitative proteomics (proteome and phosphoproteome) using a super SILAC / spiked in strategy across 38 flash frozen primary human MBs (5 WNT, 10 SHH, 10 Group 3 and 13 Group 4). First, our data pinpointed that proteomic analysis could reveal MB subgroup identity. Second, analysis of proteome and phosphoproteome highlighted disregulated signaling pathways that have not been predicted by transcriptomic analysis. Altogether, combined multi-scale analyses of MB have allowed us to identify unrevealed pathways involved in human MB genesis and progression.