• Deep proteomic profiling reveals mechanistic differences among medulloblastomas
• Proteomic-defined SHH subtypes do not differ in RNA expression
• MYC phosphorylation events define a higher risk subset of group 3 patients
• Inhibiting PRKDC may sensitize MYC-activated medulloblastoma tumors to radiation
Archer et al. quantitatively profile global proteomes of medulloblastomas ( MB).They identify different pathways associated with subsets of SHH MB and post-translational modifications of MYC associated with poor outcomes in group 3 MB. Inhibition of PRKDC sensitizes MYC-driven cells to radiation.
There is a pressing need to identify therapeutic targets in tumors with low mutation rates such as the malignant pediatric brain tumor medulloblastoma.
To address this challenge, we quantitatively profiled global proteomes
and phospho-proteomes of 45 medulloblastoma samples. Integrated analyses revealed that tumors with similar RNA expression vary extensively at the post-transcriptional and post-translational levels.
We identified distinct pathways associated with two subsets of SHH tumors, and found post-translational modifications of MYC that are associated with poor outcomes in group 3 tumors. We found kinases associated with subtypes and showed that inhibiting PRKDC sensitizes MYC-driven cells to radiation.
Our study shows that proteomics enables a more comprehensive, functional readout, providing a foundation for future therapeutic