@article{316e59a2daa443f0bf882cf182e6c2d9,
title = "Proteomics, Post-translational Modifications, and Integrative Analyses Reveal Molecular Heterogeneity within Medulloblastoma Subgroups",
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. Archer et al. quantitatively profile global proteomes of medulloblastomas (MB). They identify different pathways associated with subsets of SHH MB and post-translational modifications of MYC associated with poor outcomes in group 3 MB. Inhibition of PRKDC sensitizes MYC-driven cells to radiation.",
keywords = "MYC, NU-7441, SHH, mass spectrometry, medulloblastoma, multi-omics, network integration, phospho-proteomics, proteo-genomics, radio sensitization",
author = "Archer, {Tenley C.} and Tobias Ehrenberger and Filip Mundt and Gold, {Maxwell P.} and Karsten Krug and Mah, {Clarence K.} and Mahoney, {Elizabeth L.} and Daniel, {Colin J.} and Alexander LeNail and Divya Ramamoorthy and Philipp Mertins and Mani, {D. R.} and Hailei Zhang and Gillette, {Michael A.} and Karl Clauser and Michael Noble and Tang, {Lauren C.} and Jessica Pierre-Fran{\c c}ois and Jacob Silterra and James Jensen and Pablo Tamayo and Andrey Korshunov and Pfister, {Stefan M.} and Marcel Kool and Northcott, {Paul A.} and Sears, {Rosalie C.} and Lipton, {Jonathan O.} and Carr, {Steven A.} and Mesirov, {Jill P.} and Pomeroy, {Scott L.} and Ernest Fraenkel",
note = "Funding Information: Funding: NIH/NCI U01-CA184898 (to E.F., J.P.M., and S.L.P.), NIH/NICHD U54-HD090255 (to S.L.P.), NIH/NCI R01-CA109467 (to S.L.P. and J.P.M.), NIH/NCI R01-CA121941 (to J.P.M.), NIH/NIGMS R01-GM074024 (to J.P.M.), NIH/NCI U24-CA194107 (to J.P.M.), NIH/NCI U24-CA210004 (to J.P.M.), NIH/NCI U01-CA217885 (to J.P.M. and P.T.), NIH/NCI R01-CA154480 (to P.T.), NIH/NCI U24-CA210986 (to S.A.C. and M.A.G.), NIH/NCI U24-CA210979 (to D.R.M.), NIH/NHLBI T32-HL007901 (to T.C.A.), NIH/NICHD 1U54HD090255 ( Boston Children's Hospital IDDRC ), NIH/NCI R01-CA196228 (to R.C.S.), NIH/NCI R01-CA186241 (to R.C.S.), NIH/NCI U54-CA209988 (to R.C.S.), Swedish Research Council Dnr 2014-323 (to F.M.), Swedish Society for Medical Research (to F.M.), AACR NextGen Grant for Transformative Cancer Research (to P.A.N.), American Lebanese Syrian Associated Charities (to P.A.N.), St. Jude Children's Research Hospital (to P.A.N.), and ICGC . ",
year = "2018",
month = sep,
day = "10",
doi = "10.1016/j.ccell.2018.08.004",
language = "English (US)",
volume = "34",
pages = "396--410.e8",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "3",
}