%0 Journal Article
%T Splicing Programs and Cancer
%A Sophie Germann
%A Lise Gratadou
%A Martin Dutertre
%A Didier Auboeuf
%J Journal of Nucleic Acids
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/269570
%X Numerous studies report splicing alterations in a multitude of cancers by using gene-by-gene analysis. However, understanding of the role of alternative splicing in cancer is now reaching a new level, thanks to the use of novel technologies allowing the analysis of splicing at a large-scale level. Genome-wide analyses of alternative splicing indicate that splicing alterations can affect the products of gene networks involved in key cellular programs. In addition, many splicing variants identified as being misregulated in cancer are expressed in normal tissues. These observations suggest that splicing programs contribute to specific cellular programs that are altered during cancer initiation and progression. Supporting this model, recent studies have identified splicing factors controlling cancer-associated splicing programs. The characterization of splicing programs and their regulation by splicing factors will allow a better understanding of the genetic mechanisms involved in cancer initiation and progression and the development of new therapeutic targets. 1. Introduction Each cellular program results from the expression of gene networks or transcriptional programs that are under the control of transcription factors. However, human genes can no longer be considered as simple functional units producing a single transcript. Rather, human genes are an assemblage of exons that can be differentially selected through the use of alternative promoters, alternative polyadenylation sites, and alternatively spliced exons (Figure 1). Genome-wide analyses of splicing based on ESTs (expressed sequence tags), splicing sensitive microarrays, or deep sequencing data sets have revealed that most, if not all human genes can generate different transcripts with different exon content and there are at least 10 times more mRNAs than genes [1¨C4]. It is now widely accepted that different cell types not only differ because they express different sets of genes but also because genes produce different splicing variants depending on cell type [3, 5¨C10]. Furthermore, coordinated regulation of alternative splicing of gene products within gene networks plays a key role during differentiation [11¨C13]. Therefore, an emerging model is that each cell type at a specific developmental stage is characterized by splicing programs that together, with other layers of gene expression programs (e.g., transcriptional programs), determine the precise nature of their transcriptome and therefore their proteome. Figure 1: Genes are an assemblage of exons that can be differentially selected through
%U http://www.hindawi.com/journals/jna/2012/269570/