Proteomic Changes Resulting from Gene Copy Number Variations in Cancer Cells 英文参考文献.docVIP

ProteomicChangesResultingfromGeneCopyNumber VariationsinCancerCells TamarGeiger,JuergenCox,MatthiasMann* DepartmentforProteomicsandSignalTransduction,Max-PlanckInstituteforBiochemistry,Martinsried,Germany Abstract Along the transformation process, cells accumulate DNA aberrations, including mutations, translocations, amplifications, and deletions. Despite numerous studies, the overall effects of amplifications and deletions on the end point of gene expression—the level of proteins—is generally unknown. Here we use large-scale and high-resolution proteomics combinedwithgenecopynumberanalysistoinvestigateinaglobalmannertowhatextentthesegenomicchangeshavea proteomic output and therefore the ability to affect cellular transformation. We accurately measure expression levels of 6,735proteinsanddirectlycomparethemtothegenecopynumber.Wefindthattheaverageeffectofthesealterationson theproteinexpressionisonlyafewpercent.Nevertheless,byusinganovelalgorithm,wefindthecombinedimpactthat manyoftheseregionalchromosomalaberrationshaveattheproteinlevel.Weshowthatproteinsencodedbyamplified oncogenes are often overexpressed, while adjacent amplified genes, which presumably do not promote growth and survival, are attenuated. Furthermore, regulation of biological processes and molecular complexes is independent of general copy number changes. By connecting the primary genome alteration to their proteomic consequences, this approachhelpstointerpretthedatafromlarge-scalecancergenomicsefforts. Citation: Geiger T, Cox J, Mann M (2010) Proteomic Changes Resulting from Gene Copy Number Variations in Cancer Cells. PLoS Genet 6(9): e1001090. doi:10.1371/journal.pgen.1001090 Editor:MichaelSnyder,StanfordUniversitySchoolofMedicine,UnitedStatesofAmerica ReceivedMarch16,2010;AcceptedJuly26,2010;PublishedSeptember2,2010 Copyright: ? 2010 Geiger et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,and