title: A large scale survey reveals that chromosomal copy-number alterations significantly affect gene modules involved in cancer initiation and progression.
abstract: BACKGROUND
  Recent observations point towards the existence of a large number of neighborhoods composed of functionally-related gene modules that lie together in the genome. This local component in the distribution of the functionality across chromosomes is probably affecting the own chromosomal architecture by limiting the possibilities in which genes can be arranged and distributed across the genome. As a direct consequence of this fact it is therefore presumable that diseases such as cancer, harboring DNA copy number alterations (CNAs), will have a symptomatology strongly dependent on modules of functionally-related genes rather than on a unique "important" gene.
  
  
  METHODS
  We carried out a systematic analysis of more than 140,000 observations of CNAs in cancers and searched by enrichments in gene functional modules associated to high frequencies of loss or gains.
  
  
  RESULTS
  The analysis of CNAs in cancers clearly demonstrates the existence of a significant pattern of loss of gene modules functionally related to cancer initiation and progression along with the amplification of modules of genes related to unspecific defense against xenobiotics (probably chemotherapeutical agents). With the extension of this analysis to an Array-CGH dataset (glioblastomas) from The Cancer Genome Atlas we demonstrate the validity of this approach to investigate the functional impact of CNAs.
  
  
  CONCLUSIONS
  The presented results indicate promising clinical and therapeutic implications. Our findings also directly point out to the necessity of adopting a function-centric, rather a gene-centric, view in the understanding of phenotypes or diseases harboring CNAs.
authors.affiliation: Department of Bioinformatics and Genomics, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Alloza
authors.forename: Fátima
authors.initials: F
authors.lastname: Al-Shahrour
authors.forename: Juan C
authors.initials: JC
authors.lastname: Cigudosa
authors.forename: Joaquín
authors.initials: J
authors.lastname: Dopazo
mesh_terms: D001686:Biological Phenomena / Q000235:genetics; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations / Q000235:genetics*; D003625:Data Collection; D018450:Disease Progression; D053263:Gene Regulatory Networks / Q000235:genetics*; D052138:Genes, Neoplasm / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D011230:Precancerous Conditions / Q000235:genetics*; D015203:Reproducibility of Results