Journal Article

DKFZ-2018-01520

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Proteomics, Post-translational Modifications, and Integrative Analyses Reveal Molecular Heterogeneity within Medulloblastoma Subgroups.

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.DKFZ* ; Pfister, S.DKFZ* ; Kool, M.DKFZ* ; Northcott, P. A.DKFZ* ; Sears, R. C. ; Lipton, J. O. ; Carr, S. A. ; Mesirov, J. P. ; Pomeroy, S. L. ; Fraenkel, E.

2018
Cell Press Cambridge, Mass.

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Please use a persistent id in citations: doi:10.1016/j.ccell.2018.08.004

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.

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Contributing Institute(s):

1. KKE Neuropathologie (G380)
2. Pädiatrische Neuroonkologie (B062)
3. DKTK Heidelberg (L101)

Research Program(s):

1. 319H - Addenda (POF3-319H) (POF3-319H)

Appears in the scientific report 2018

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Database coverage:
; BIOSIS Previews ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 20 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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