Chimeric RNAs in cancer

Abstract

Chimeric RNAs are hybrid transcripts containing exons from two separate genes. Chimeric RNAs are traditionally considered to be transcribed from fusion genes caused by chromosomal rearrangement. These canonical chimeric RNAs are well characterized to be expressed in a cancer-unique pattern and/or act as oncogene products. However, benefited by the development of advanced deep sequencing technologies, novel types of non-canonical chimeric RNAs have been discovered to be generated from intergenic splicing without genomic aberrations. They can be formed through trans-splicing or cis-splicing between adjacent genes (cis-SAGe) mechanisms. Non-canonical chimeric RNAs are widely detected in normal physiology, although several have been shown to have a cancer-specific expression pattern. Further studies have indicated that some of them play fundamental roles in controlling cell growth and motility, and may have functions independent of the parental genes. These discoveries are unveiling a new layer of the functional transcriptome and are also raising the possibility of utilizing non-canonical chimeric RNAs as cancer diagnostic markers and therapeutic targets. In this chapter, we will overview different categories of chimeric RNAs and their expression in various types of cancerous and normal samples. Acknowledging that chimeric RNAs are not unique to cancer, we will discuss both bioinformatic and biological methods to identify credible cancer-specific chimeric RNAs. Furthermore, we will describe downstream methods to explore their molecular processing mechanisms and potential functions. A better understanding of the biogenesis mechanisms and functional products of cancer-specific chimeric RNAs will pave ways for the development of novel cancer biomarkers and therapeutic targets.

Keywords: Cancer; Chimeric RNA; Chromosomal rearrangement; Cis-splicing between adjacent genes (cis-SAGe); Fusion gene; Trans-splicing.