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Proteomics, post-translational modifications, and integrative analyses reveal molecular heterogeneity within medulloblastoma subgroups

Item Type:Article
Title:Proteomics, post-translational modifications, and integrative analyses reveal molecular heterogeneity within medulloblastoma subgroups
Creators Name:Archer, T.C., Ehrenberger, T., Mundt, F., Gold, M.P., Krug, K., Mah, C.K., Mahoney, E.L., Daniel, C.J., LeNail, A., Ramamoorthy, D., Mertins, P., Mani, D.R., Zhang, H., Gillette, M.A., Clauser, K., Noble, M., Tang, L.C., Pierre-François, J., Silterra, J., Jensen, J., Tamayo, P., Korshunov, A., Pfister, S.M., Kool, M., Northcott, P.A., Sears, R.C., Lipton, J.O., Carr, S.A., Mesirov, J.P., Pomeroy, S.L. and Fraenkel, E.
Abstract: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 strategies.
Keywords:Medulloblastoma, Mass Spectrometry, Phospho-Proteomics, Multi-Omics, SHH, MYC, Proteo-Genomics, Radio Sensitization, Network Integration, NU-7441
Source:Cancer Cell
ISSN:1535-6108
Publisher:Cell Press / Elsevier
Volume:34
Number:3
Page Range:396-410
Date:10 September 2018
Official Publication:https://doi.org/10.1016/j.ccell.2018.08.004
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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