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@ARTICLE{Staal:127545,
author = {J. A. Staal and L. S. Lau and H. Zhang and W. J. Ingram and
A. R. Hallahan and P. A. Northcott$^*$ and S. Pfister$^*$
and R. J. Wechsler-Reya and J. M. Rusert and M. D. Taylor
and Y.-J. Cho and R. J. Packer and K. J. Brown and B. R.
Rood},
title = {{P}roteomic profiling of high risk medulloblastoma reveals
functional biology.},
journal = {OncoTarget},
volume = {6},
number = {16},
issn = {1949-2553},
address = {[S.l.]},
publisher = {Impact Journals LLC},
reportid = {DKFZ-2017-03568},
pages = {14584 - 14595},
year = {2015},
abstract = {Genomic characterization of medulloblastoma has improved
molecular risk classification but struggles to define
functional biological processes, particularly for the most
aggressive subgroups. We present here a novel proteomic
approach to this problem using a reference library of stable
isotope labeled medulloblastoma-specific proteins as a
spike-in standard for accurate quantification of the tumor
proteome. Utilizing high-resolution mass spectrometry, we
quantified the tumor proteome of group 3 medulloblastoma
cells and demonstrate that high-risk MYC amplified tumors
can be segregated based on protein expression patterns. We
cross-validated the differentially expressed protein
candidates using an independent transcriptomic data set and
further confirmed them in a separate cohort of
medulloblastoma tissue samples to identify the most robust
proteogenomic differences. Interestingly, highly expressed
proteins associated with MYC-amplified tumors were
significantly related to glycolytic metabolic pathways via
alternative splicing of pyruvate kinase (PKM) by
heterogeneous ribonucleoproteins (HNRNPs). Furthermore, when
maintained under hypoxic conditions, these MYC-amplified
tumors demonstrated increased viability compared to
non-amplified tumors within the same subgroup. Taken
together, these findings highlight the power of proteomics
as an integrative platform to help prioritize genetic and
molecular drivers of cancer biology and behavior.},
keywords = {Biomarkers, Tumor (NLM Chemicals)},
cin = {B062},
ddc = {610},
cid = {I:(DE-He78)B062-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25970789},
pmc = {pmc:PMC4546489},
doi = {10.18632/oncotarget.3927},
url = {https://inrepo02.dkfz.de/record/127545},
}