论文部分内容阅读
Gene fusions have long been considered hallmarks of cancer.Efforts into characterization of their prevalence, cause, and function have provided significant progress toward improve-ments in diagnosis, prognosis assessment, and treatment of numerous cancers. More recently, detection of intergenically spliced chimeric RNAs in cancer has spurred efforts to charac-terize these transcripts, anticipating similar successes in trans-lation to the clinic. Discovery of chimeric RNAs in normal cells,especially those which precede canonical translocations such as PAX3-FOX01 and JAZF1-JJAZ1, suggests that these physiologically regulated transcripts may function as proto-oncogenic factors, in that their dysregulation can lead to cancer progression. These findings have given rise to conjecture regarding chimeric RNA-guided rearrangements giving rise to fusion genes, termed the cart-before-the-horse hypothesis. Here, we provide context for the relationship between gene fusions, chimeric RNAs, and can-cer; assemble evidence in support of the cart-before-the-horse hypothesis; and discuss potential advantages of targeting chimeric RNAs in cancer treatment.