Digging in the RNA-seq Garbage: Evaluating the Characteristics of Unmapped RNA-seq Reads in Normal Tissues

RNA-seq has the potential to discover genes created by complex chromosomal rearrangements. ´Fusion´ genes formed by the breakage and re-joining of two different chromosomes have repeatedly been implicated in the development of cancer. However, although RNA-seq can detect these fusion events, normal cells are also characterized by read-through fusions across adjacent genes in the genome, or by transcription-induced chimeras (TICs). In this paper, we detected TICs events in normal tissue samples. The information derived from our analysis indicates the presence of a significant number of TICs in normal tissues. Some of these TICs can be associated with cancer development. In some cases TIC expression is corroborated by a large number of reads and their expression is significantly spread over different tissues. Our data highlight that TICs could be erroneously associated with cancer aberrations if RNA-seq analysis is only evaluated in tumor samples without considering the parallel analysis of normal tissue samples associated with the tumor.