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bioRxiv · 10.1101/162560

A comprehensive characterization of cis-acting splicing-associated variants in human cancer

Shiraishi, Y.·Kataoka, K.·Chiba, K.·Okada, A.·Koure, Y.·Tanaka, H.·Ogawa, S.·Miyano, S.
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Abstract

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.

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Shiraishi, Y., Kataoka, K., Chiba, K., Okada, A., Koure, Y., Tanaka, H., Ogawa, S., Miyano, S.. 2017-07-13. A comprehensive characterization of cis-acting splicing-associated variants in human cancer. https://doi.org/10.1101/162560

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