Genome-wide co-localization of RNA-DNA interactions and fusion RNA pairs (RNAseq)

Despite the ever-increasing speed of detecting fusion transcripts in cancer, it remains formidable to predict what unreported RNA pairs can form new fusion transcripts. By systematic mapping of chromatin-associated RNAs (caRNAs) and their respective genomic interaction loci, we obtained genome-wide RNA-DNA interaction maps from two non-cancerous cell types. The gene pairs involved in RNA-DNA interactions in these normal cells exhibited strong overlap with those with cancer-derived fusion transcripts. These data suggest an RNA-poise model, where the spatial proximity of one gene’s transcripts and the other gene’s genomic sequence poises for the creation of fusion transcripts. We validated this model with 96 additional lung cancer samples. One of these additional samples exhibited fusion transcripts without a corresponding fusion gene, suggesting that genome-recombination is not a required step of the RNA-poise model. Targeted RNA-seq on lung cancer patient biopsy and H2228 cell line