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

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 reve...

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Main Authors: Archer, Tenley C. (Author) , Ehrenberger, Tobias (Author) , Mundt, Filip (Author) , Gold, Maxwell P. (Author) , Krug, Karsten (Author) , Mah, Clarence K. (Author) , Mahoney, Elizabeth L. (Author) , Daniel, Colin J. (Author) , LeNail, Alexander (Author) , Ramamoorthy, Divya (Author) , Mertins, Philipp (Author) , Mani, D. R. (Author) , Zhang, Hailei (Author) , Gillette, Michael A. (Author) , Clauser, Karl (Author) , Noble, Michael (Author) , Tang, Lauren C. (Author) , Pierre-François, Jessica (Author) , Silterra, Jacob (Author) , Jensen, James (Author) , Tamayo, Pablo (Author) , Korshunov, Andrey (Author) , Pfister, Stefan (Author) , Kool, Marcel (Author) , Northcott, Paul A. (Author) , Sears, Rosalie C. (Author) , Lipton, Jonathan O. (Author) , Carr, Steven A. (Author) , Mesirov, Jill P. (Author) , Pomeroy, Scott L. (Author) , Fraenkel, Ernest (Author)
Format: Article (Journal)
Language:English
Published: September 10, 2018
In: Cancer cell
Year: 2018, Volume: 34, Issue: 3, Pages: 396-410, e1-e8
ISSN:1878-3686
DOI:10.1016/j.ccell.2018.08.004
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ccell.2018.08.004
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S1535610818303581
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Author Notes:Tenley C. Archer, Tobias Ehrenberger, Filip Mundt, Maxwell P. Gold, Karsten Krug, Clarence K. Mah, Elizabeth L. Mahoney, Colin J. Daniel, Alexander LeNail, Divya Ramamoorthy, Philipp Mertins, D. R. Mani, Hailei Zhang, Michael A. Gillette, Karl Clauser, Michael Noble, Lauren C. Tang, Jessica Pierre-François, Jacob Silterra, James Jensen, Pablo Tamayo, Andrey Korshunov, Stefan M. Pfister, Marcel Kool, Paul A. Northcott, Rosalie C. Sears, Jonathan O. Lipton, Steven A. Carr, Jill P. Mesirov, Scott L. Pomeroy, and Ernest Fraenkel
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Summary: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.
Item Description:Gesehen am 03.06.2020
Physical Description:Online Resource
ISSN:1878-3686
DOI:10.1016/j.ccell.2018.08.004

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