title: Proteomic changes resulting from gene copy number variations in cancer cells.
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 combined with gene copy number analysis to investigate in a global manner to what extent these genomic changes have a proteomic output and therefore the ability to affect cellular transformation. We accurately measure expression levels of 6,735 proteins and directly compare them to the gene copy number. We find that the average effect of these alterations on the protein expression is only a few percent. Nevertheless, by using a novel algorithm, we find the combined impact that many of these regional chromosomal aberrations have at the protein level. We show that proteins encoded by amplified 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 approach helps to interpret the data from large-scale cancer genomics efforts.
authors.affiliation: Department for Proteomics and Signal Transduction, Max-Planck Institute for Biochemistry, Martinsried, Germany.
authors.forename: Tamar
authors.initials: T
authors.lastname: Geiger
authors.forename: Juergen
authors.initials: J
authors.lastname: Cox
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D002460:Cell Line; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations / Q000235:genetics*; D030541:Databases, Genetic; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D055550:Protein Stability; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D020543:Proteome; D012333:RNA, Messenger; D046988:Proteasome Endopeptidase Complex
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