ABSTRACT: Archer TC, Ehrenberger T, Mundt F, Gold MP, Krug K, Mah CK, Mahoney EL, Daniel CJ, LeNail A, Ramamoorthy D, Mertins P, Mani DR, Zhang H, Gillette MA, Clauser K, Noble M, Tang LC, Francois JP, Silterra J, Jensen J, Tamayo P, Korshunov A, Pfister SM, Kool M, Northcott PA, Sears RC, Lipton JO, Carr SA, Mesirov JP, Pomeroy SL, Fraenkel E. Cancer Cell 2018.
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 tumors to radiation. Our study shows that proteomics enables a more comprehensive, functional readout, providing a foundation for new therapeutic strategies.
Steven A. Carr 