title: Aberrant RNA splicing in cancer; expression changes and driver mutations of splicing factor genes.
abstract: Alternative splicing is a widespread process contributing to structural transcript variation and proteome diversity. In cancer, the splicing process is commonly disrupted, resulting in both functional and non-functional end-products. Cancer-specific splicing events are known to contribute to disease progression; however, the dysregulated splicing patterns found on a genome-wide scale have until recently been less well-studied. In this review, we provide an overview of aberrant RNA splicing and its regulation in cancer. We then focus on the executors of the splicing process. Based on a comprehensive catalog of splicing factor encoding genes and analyses of available gene expression and somatic mutation data, we identify cancer-associated patterns of dysregulation. Splicing factor genes are shown to be significantly differentially expressed between cancer and corresponding normal samples, and to have reduced inter-individual expression variation in cancer. Furthermore, we identify enrichment of predicted cancer-critical genes among the splicing factors. In addition to previously described oncogenic splicing factor genes, we propose 24 novel cancer-critical splicing factors predicted from somatic mutations.
authors: Department of Molecular Oncology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.|K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway.|Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors: A
authors: A
authors: Sveen
authors: MediSapiens Ltd., Helsinki, Finland.
authors: S
authors: S
authors: Kilpinen
authors: MediSapiens Ltd., Helsinki, Finland.
authors: A
authors: A
authors: Ruusulehto
authors: Department of Molecular Oncology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.|K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway.|Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors: R A
authors: RA
authors: Lothe
authors: Department of Molecular Oncology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.|K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway.|Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors: R I
authors: RI
authors: Skotheim
mesh_terms: D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D000072260:RNA Splicing Factors / Q000235:genetics*
chemical_list: D000072260:RNA Splicing Factors