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000136037 1001_ $$aRivero-Hinojosa, Samuel$$b0
000136037 245__ $$aProteomic analysis of Medulloblastoma reveals functional biology with translational potential.
000136037 260__ $$aLondon$$bBiomed Central$$c2018
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000136037 520__ $$aGenomic characterization has begun to redefine diagnostic classifications of cancers. However, it remains a challenge to infer disease phenotypes from genomic alterations alone. To help realize the promise of genomics, we have performed a quantitative proteomics investigation using Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and 41 tissue samples spanning the 4 genomically based subgroups of medulloblastoma and control cerebellum. We have identified and quantitated thousands of proteins across these groups and find that we are able to recapitulate the genomic subgroups based upon subgroup restricted and differentially abundant proteins while also identifying subgroup specific protein isoforms. Integrating our proteomic measurements with genomic data, we calculate a poor correlation between mRNA and protein abundance. Using EPIC 850 k methylation array data on the same tissues, we also investigate the influence of copy number alterations and DNA methylation on the proteome in an attempt to characterize the impact of these genetic features on the proteome. Reciprocally, we are able to use the proteome to identify which genomic alterations result in altered protein abundance and thus are most likely to impact biology. Finally, we are able to assemble protein-based pathways yielding potential avenues for clinical intervention. From these, we validate the EIF4F cap-dependent translation pathway as a novel druggable pathway in medulloblastoma. Thus, quantitative proteomics complements genomic platforms to yield a more complete understanding of functional tumor biology and identify novel therapeutic targets for medulloblastoma.
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000136037 7001_ $$aLau, Ling San$$b1
000136037 7001_ $$aStampar, Mojca$$b2
000136037 7001_ $$aStaal, Jerome$$b3
000136037 7001_ $$aZhang, Huizhen$$b4
000136037 7001_ $$aGordish-Dressman, Heather$$b5
000136037 7001_ $$0P:(DE-HGF)0$$aNorthcott, Paul A$$b6
000136037 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b7$$udkfz
000136037 7001_ $$aTaylor, Michael D$$b8
000136037 7001_ $$aBrown, Kristy J$$b9
000136037 7001_ $$00000-0003-3221-9421$$aRood, Brian R$$b10
000136037 773__ $$0PERI:(DE-600)2715589-4$$a10.1186/s40478-018-0548-7$$gVol. 6, no. 1, p. 48$$n1$$p48$$tActa Neuropathologica Communications$$v6$$x2051-5960$$y2018
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