%0 Journal Article
%T A large scale survey reveals that chromosomal copy-number alterations significantly affect gene modules involved in cancer initiation and progression
%A Eva Alloza
%A F¨¢tima Al-Shahrour
%A Juan C Cigudosa
%A Joaqu¨ªn Dopazo
%J BMC Medical Genomics
%D 2011
%I BioMed Central
%R 10.1186/1755-8794-4-37
%X 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.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.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.For many years, research into the genetic basis of many different diseases has cumulated a large corpus of knowledge on the links between particular genes and diseases. However, most diseases are multigenic and cannot be explained or characterized by a single gene but rather by a combination of genes [1]. In a broad sense, multigenecity reflects disruptions in proteins that participate in a protein complex, in a pathway [2] or, in general, in any known or yet to be discovered functional unit or module.It is widely accepted that most of the biological functionality of the cell arises from complex interactions between their molecular components that define functional entities or modules that operate as small subcellular systems [3]. Recent evidence shows that genes mapping in close physical locations in the chromosomes tend to have a high degree of co-expression, that can often be linked to common functionality [4]. We have recently demonstrated that chromosomal regions enriched in certain types of functions have arisen at determin
%U http://www.biomedcentral.com/1755-8794/4/37