RT Journal Article
SR Electronic
T1 A comprehensive characterization of cis-acting splicing-associated variants in human cancer
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 162560
DO 10.1101/162560
A1 Yuichi Shiraishi
A1 Keisuke Kataoka
A1 Kenichi Chiba
A1 Ai Okada
A1 Yasunori Koure
A1 Hiroko Tanaka
A1 Seishi Ogawa
A1 Satoru Miyano
YR 2017
UL http://biorxiv.org/content/early/2017/07/13/162560.abstract
AB Although many driver mutations are thought to promote carcinogenesis via abnormal splicing, the landscape of these splicing-associated variants (SAVs) remains unknown due to the complexity of splicing abnormalities. Here we developed a statistical framework to identify SAVs disrupting or newly creating splice site motifs and applied it to sequencing data from 8,976 samples across 31 cancer types. We constructed a catalog of 14,438 SAVs, approximately 50% of which consist of SAVs disrupting non-canonical splice sites (including the 3rd and 5th intronic bases of donor sites) or newly creating splice sites. Smoking-related signature substantially contributes to SAV generation. As many as 14.7% of samples harbor at least one SAVs in cancer-related genes, particularly in tumor suppressors. Importantly, in addition to previously reported intron retention, exon skipping or alternative splice site usage more frequently affected these genes. Our findings delineate a comprehensive portrait of SAVs, providing a basis for cancer precision medicine.