A pan-cancer interrogation of intronic polyadenylation and its association with cancer characteristics.

Abstract

3'UTR-APAs have been extensively studied, but intronic polyadenylations (IPAs) remain largely unexplored. We characterized the profiles of 22 260 IPAs in 9679 patient samples across 32 cancer types from the Cancer Genome Atlas cohort. By comparing tumor and paired normal tissues, we identified 180 ~ 4645 dysregulated IPAs in 132 ~ 2249 genes in each of 690 patient tumors from 22 cancer types that showed consistent patterns within individual cancer types. We selected 2741 genes that showed consistently patterns across cancer types, including 1834 pan-cancer tumor-enriched and 907 tumor-depleted IPA genes; the former were amply represented in the functional pathways such as deoxyribonucleic acid damage repair. Expression of IPA isoforms was associated with tumor mutation burden and patient characteristics (e.g. sex, race, cancer stages, and subtypes) in cancer-specific and feature-specific manners, and could be a more accurate prognostic marker than gene expression (summary of all isoforms). In summary, our study reveals the roles and the clinical relevance of tumor-associated IPAs.