Chimeric RNAs generated by intergenic splicing in normal and cancer cells

Abstract

A hallmark of many neoplasias is chromosomal rearrangement, an event that commonly results in the fusion of two separate genes. The RNA and protein resulting from these gene fusions often play critical roles in cancer development, maintenance, and progression. Traditionally, these fusion products are thought to be produced solely due to DNA level changes and are therefore considered unique to cancer. Recent advances in microarray and deep-sequencing have revealed many more fusion transcripts. Surprisingly, some are without detectable rearrangement at the DNA level. Reports have demonstrated that at least some of these chimeric RNAs are generated via intergenic splicing. In this review, we highlight three examples of these noncanonical chimeric transcripts that are formed by trans-splicing or cis-splicing of adjacent genes and summarize the knowledge we have regarding these noncanonical fusions. We discuss the implications of the chimeric RNAs in both cancer and normal physiology, as some of these fusion transcripts are found in normal, noncancerous cells with sequences identical to those generated by canonical chromosomal translocation found in cancer cells. Finally, we present methods that are currently being used to discover additional chimeric RNAs.