RT Journal Article SR Electronic T1 Pan-cancer analysis reveals complex tumor-specific alternative polyadenylation JF bioRxiv FD Cold Spring Harbor Laboratory SP 160960 DO 10.1101/160960 A1 Zhuyi Xue A1 René L Warren A1 Ewan A Gibb A1 Daniel MacMillan A1 Johnathan Wong A1 Readman Chiu A1 S Austin Hammond A1 Catherine A Ennis A1 Abigail Hahn A1 Sheila Reynolds A1 Inanc Birol YR 2017 UL http://biorxiv.org/content/early/2017/07/08/160960.abstract AB Alternative polyadenylation (APA) of 3’ untranslated regions (3’ UTRs) has been implicated in cancer development. Earlier reports on APA in cancer primarily focused on 3’ UTR length modifications, and the conventional wisdom is that tumor cells preferentially express transcripts with shorter 3’ UTRs. Here, we analyzed the APA patterns of 114 genes, a select list of oncogenes and tumor suppressors, in 9,939 tumor and 729 normal tissue samples across 33 cancer types using RNA-Seq data from The Cancer Genome Atlas, and we found that the APA regulation machinery is much more complicated than what was previously thought. We report 77 cases (gene-cancer type pairs) of differential 3’ UTR cleavage patterns between normal and tumor tissues, involving 33 genes in 13 cancer types. For 15 genes, the tumor-specific cleavage patterns are recurrent across multiple cancer types. While the cleavage patterns in certain genes indicate apparent trends of 3’ UTR shortening in tumor samples, over half of the 77 cases imply 3’ UTR length change trends in cancer that are more complex than simple shortening or lengthening. This work extends the current understanding of APA regulation in cancer, and demonstrates how large volumes of RNA-seq data generated for characterizing cancer cohorts can be mined to investigate this process.