The Genomic Landscape and Clinical Relevance of A-to-I RNA Editing in Human Cancers

Adenosine-to-inosine (A-to-I) RNA editing is a widespread post-transcriptional mechanism, but its genomic landscape and clinical relevance in cancer have not been investigated systematically. We characterized the global A-to-I RNA editing profiles of 6,236 patient samples of 17 cancer types from The Cancer Genome Atlas and revealed a striking diversity of altered RNA-editing patterns in tumors relative to normal tissues. We identified an appreciable number of clinically relevant editing events, many of which are in noncoding regions. We experimentally demonstrated the effects of several cross-tumor nonsynonymous RNA editing events on cell viability and provide the evidence that RNA editing could selectively affect drug sensitivity. These results highlight RNA editing as an exciting theme for investigating cancer mechanisms, biomarkers, and treatments. [Display omitted] •A systematic analysis of genome-wide RNA editing events across tumor types was done•A considerable number of clinically relevant RNA editing events are revealed•The functional effects of cross-tumor nonsynonymous RNA editing events are shown•Evidence that nonsynonymous RNA editing may affect drug sensitivity is provided Han et al. characterize global A-to-I RNA editing profiles across 17 cancer types and experimentally demonstrate the effects of several cross-tumor nonsynonymous RNA editing events on cell viability and drug sensitivity.