![]() ![]() Importantly, these are associated with poor clinical outcomes in bladder cancer 3. For instance, recurrent mutations in the TERT promoter have been found in gliomas, melanoma, and bladder cancers 1, 2, 3. Non-coding drivers have started to emerge from whole-genome sequencing (WGS) data. Large-scale studies, such as The Cancer Genome Atlas (TCGA), have identified numerous driver mutations in coding regions using whole-exome sequencing (WES) data, but most non-coding sequences still lack characterization. MiSplice will be useful for automatically annotating the splicing impact of coding and non-coding mutations in future large-scale analyses. Our study suggests the importance of investigating biological and clinical consequences of noncoding splice-inducing mutations that were previously neglected by conventional annotation pipelines. The pattern emerging from these exon-creating mutations suggests that splice sites created by non-coding mutations interact with pre-existing potential splice sites that originally lacked a suitable splicing pair to induce new exon formation. We find that some mutation-induced splicing alterations are located in genes important in tumorigenesis ( ATRX, BCOR, CDKN2B, MAP3K1, MAP3K4, MDM2, SMAD4, STK11, TP53 etc.), often leading to truncated proteins and affecting gene expression. Introns associated with new exon creation are significantly larger than the genome-wide average intron size. Notably, most of these mutations create new exons. Here we use the MiSplice pipeline to analyze 783 cancer cases with WGS data and 9494 cases with WES data, discovering 562 non-coding mutations that lead to splicing alterations. Non-coding mutations can create splice sites, however the true extent of how such somatic non-coding mutations affect RNA splicing are largely unexplored. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |