Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
Hum Mol Genet. 2011 Nov 15;20(22):4422-9. doi: 10.1093/hmg/ddr370. Epub 2011 Aug 23.
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.
最近的全基因组分析检测到了许多癌症特异性的可变剪接 (AS) 事件。目前尚不清楚包含癌症特异性 AS 事件的转录本是否更有可能被翻译为功能性蛋白质，还是仅仅反映了嘈杂的剪接，从而决定其临床相关性。在这里，我们表明，与嘈杂剪接模型一致，癌症特异性 AS 事件通常倾向于罕见，在人和小鼠中含有更多的过早终止密码子，并且功能结构域的可识别性更低。有趣的是，来自肿瘤抑制基因和癌基因的常见癌症衍生的 AS 转录本显示出明显的过早终止密码子频率变化；肿瘤抑制基因中过早终止密码子的水平增加，而癌基因则相反。我们得出的结论是，肿瘤倾向于具有忠实的癌基因剪接，并且在具有肿瘤抑制基因和癌症特异性剪接变异体的更高比例的过早终止密码子中显示出考虑剪接噪声在分析癌症特异性剪接变化时的重要性。
