title: Increased levels of noisy splicing in cancers, but not for oncogene-derived transcripts.
abstract: Recent genome-wide analyses have detected numerous cancer-specific alternative splicing (AS) events. Whether transcripts containing cancer-specific AS events are likely to be translated into functional proteins or simply reflect noisy splicing, thereby determining their clinical relevance, is not known. Here we show that consistent with a noisy-splicing model, cancer-specific AS events generally tend to be rare, containing more premature stop codons and have less identifiable functional domains in both the human and mouse. Interestingly, common cancer-derived AS transcripts from tumour suppressor and oncogenes show marked changes in premature stop-codon frequency; with tumour suppressor genes exhibiting increased levels of premature stop codons whereas oncogenes have the opposite pattern. We conclude that tumours tend to have faithful oncogene splicing and a higher incidence of premature stop codons among tumour suppressor and cancer-specific splice variants showing the importance of considering splicing noise when analysing cancer-specific splicing changes.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Tovar-Corona
authors.forename: Araxi O
authors.initials: AO
authors.lastname: Urrutia
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*