RNA splicing factors as oncoproteins and tumour suppressors

H Dvinge, E Kim, O Abdel-Wahab… - Nature Reviews Cancer, 2016 - nature.com
H Dvinge, E Kim, O Abdel-Wahab, RK Bradley
Nature Reviews Cancer, 2016nature.com
The recent genomic characterization of cancers has revealed recurrent somatic point
mutations and copy number changes affecting genes encoding RNA splicing factors. Initial
studies of these'spliceosomal mutations' suggest that the proteins bearing these mutations
exhibit altered splice site and/or exon recognition preferences relative to their wild-type
counterparts, resulting in cancer-specific mis-splicing. Such changes in the splicing
machinery may create novel vulnerabilities in cancer cells that can be therapeutically …
Abstract
The recent genomic characterization of cancers has revealed recurrent somatic point mutations and copy number changes affecting genes encoding RNA splicing factors. Initial studies of these 'spliceosomal mutations' suggest that the proteins bearing these mutations exhibit altered splice site and/or exon recognition preferences relative to their wild-type counterparts, resulting in cancer-specific mis-splicing. Such changes in the splicing machinery may create novel vulnerabilities in cancer cells that can be therapeutically exploited using compounds that can influence the splicing process. Further studies to dissect the biochemical, genomic and biological effects of spliceosomal mutations are crucial for the development of cancer therapies targeted at these mutations.
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