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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. and Ehrenberger, T. and Mundt, F. and Gold, M.P. and Krug, K. and Mah, C.K. and Mahoney, E.L. and Daniel, C.J. and LeNail, A. and Ramamoorthy, D. and Mertins, P. and Mani, D.R. and Zhang, H. and Gillette, M.A. and Clauser, K. and Noble, M. and Tang, L.C. and Pierre-François, J. and Silterra, J. and Jensen, J. and Tamayo, P. and Korshunov, A. and Pfister, S.M. and Kool, M. and Northcott, P.A. and Sears, R.C. and Lipton, J.O. and Carr, S.A. and Mesirov, J.P. and 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:Elsevier / Cell Press (U.S.A.)
Volume:34
Number:3
Page Range:396-410
Date:10 September 2018
Official Publication:https://doi.org/10.1016/j.ccell.2018.08.004
PubMed:View item in PubMed

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