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@ARTICLE{RiveroHinojosa:136037,
author = {S. Rivero-Hinojosa and L. S. Lau and M. Stampar and J.
Staal and H. Zhang and H. Gordish-Dressman and P. A.
Northcott$^*$ and S. Pfister$^*$ and M. D. Taylor and K. J.
Brown and B. R. Rood},
title = {{P}roteomic analysis of {M}edulloblastoma reveals
functional biology with translational potential.},
journal = {Acta Neuropathologica Communications},
volume = {6},
number = {1},
issn = {2051-5960},
address = {London},
publisher = {Biomed Central},
reportid = {DKFZ-2018-00736},
pages = {48},
year = {2018},
abstract = {Genomic characterization has begun to redefine diagnostic
classifications of cancers. However, it remains a challenge
to infer disease phenotypes from genomic alterations alone.
To help realize the promise of genomics, we have performed a
quantitative proteomics investigation using Stable Isotope
Labeling by Amino Acids in Cell Culture (SILAC) and 41
tissue samples spanning the 4 genomically based subgroups of
medulloblastoma and control cerebellum. We have identified
and quantitated thousands of proteins across these groups
and find that we are able to recapitulate the genomic
subgroups based upon subgroup restricted and differentially
abundant proteins while also identifying subgroup specific
protein isoforms. Integrating our proteomic measurements
with genomic data, we calculate a poor correlation between
mRNA and protein abundance. Using EPIC 850 k methylation
array data on the same tissues, we also investigate the
influence of copy number alterations and DNA methylation on
the proteome in an attempt to characterize the impact of
these genetic features on the proteome. Reciprocally, we are
able to use the proteome to identify which genomic
alterations result in altered protein abundance and thus are
most likely to impact biology. Finally, we are able to
assemble protein-based pathways yielding potential avenues
for clinical intervention. From these, we validate the EIF4F
cap-dependent translation pathway as a novel druggable
pathway in medulloblastoma. Thus, quantitative proteomics
complements genomic platforms to yield a more complete
understanding of functional tumor biology and identify novel
therapeutic targets for medulloblastoma.},
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:29880060},
doi = {10.1186/s40478-018-0548-7},
url = {https://inrepo02.dkfz.de/record/136037},
}