Proteomics, Post-translational Modifications, and Integrative Analyses Reveal Molecular Heterogeneity within Medulloblastoma Subgroups
Name
nihms-1503512.pdf
Description
Accepted version
Size
1.77 MB
Format
Adobe PDF
Checksum (MD5)
7ba94fd7320d01dbe8a43df4355dc783
Author(s)
Ehrenberger, Tobias
Gold, Maxwell P.
LeNail, Alexander
Ramamoorthy, Divya
Fraenkel, Ernest
Date Issued
September 2018
Journal
Cancer Cell
Publisher
Elsevier BV
Citation
Archer, Tenley C. et al. “Proteomics, Post-translational Modifications, and Integrative Analyses Reveal Molecular Heterogeneity within Medulloblastoma Subgroups.” Cancer cell 34 (2019): 396-410 © 2019 The Author(s)
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.ccell.2018.08.004
