PT  - JOURNAL ARTICLE
AU  - Yuichi Shiraishi
AU  - Keisuke Kataoka
AU  - Kenichi Chiba
AU  - Ai Okada
AU  - Yasunori Kogure
AU  - Hiroko Tanaka
AU  - Seishi Ogawa
AU  - Satoru Miyano
TI  - A comprehensive characterization of cis-acting splicing-associated variants in human cancer
AID  - 10.1101/162560
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 162560
4099  - http://biorxiv.org/content/early/2017/09/28/162560.short
4100  - http://biorxiv.org/content/early/2017/09/28/162560.full
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.