Fusion RNA Profiling in Cancer: Investigating the Etiology of Fusion-Gene-Associated Cancers and Proposing an Approach to Study Connections Between Biological Samples.

Gene fusions were thought to be unique features of neoplasia. However, more and more studies have identified fusion RNAs in normal physiology. Through RNA sequencing of human normal tissues from GTEx project, many chimeric RNAs were found. By analyzing the fusion transcriptome, we observed a close cluster between samples of the same or similar tissues, supporting the feasibility of using fusion RNA profiling to reveal connections between biological samples. To put the concept into use, we selected alveolar rhabdomyosarcoma (ARMS), a myogenic pediatric cancer whose exact cell of origin is not clear. PAX3-FOXO1 fusion RNA, which is considered a hallmark of ARMS, was found during normal muscle cell differentiation. We analyzed RNA sequencing from various time points during myogenesis and uncovered many chimeric fusion RNAs.