Case Study: Landscape of Chimeric RNAs in Bladder Cancer
Chimeric RNAs and their products have been shown to be closely associated with tumorigenicity and development in a variety of tumors, making them attractive diagnostic markers and therapeutic targets. In previous chapters, we introduced related research techniques and methods for studying chimeric RNAs. Here, we present an overview of the landscape of chimeric RNAs in bladder cancer and verification of two fusion transcripts which are associated with bladder cancer. We used bioinformatics to analyze the TCGA bladder urothelial carcinoma RNA-sequencing dataset, which contains 414 bladder cancer samples and 19 matched normal samples. We identified 19,547 chimeric RNAs and applied multiple criteria to avoid false positives, reducing this list to 271 high-confidence chimeric RNAs, 13 of which specifically expressed in cancer. We validated 6 of these chimeric in clinical bladder cancer samples, including CHFR-GOLGA3, which was found to be expressed significantly higher in bladder cancer samples in comparison to matched normal samples. We have determined that this chimeric RNA is produced by cis-splicing between adjacent genes (cis-SAGe). Further, we found that CHFR-GOLGA3 is mainly expressed in the nucleus, suggesting that it may not encode chimeric protein and instead act as noncoding RNA. Our findings establish the chimeric landscape of bladder cancer and provide a research strategy for how to conduct chimeric RNA research in other tumors.
Key wordsChimeric RNAs Gene fusion Bladder cancer Intergenic cis-splicing
This work was supported by NIH NCI grant CA190713 (HL). We thank the Biorepository and Tissue Research Facility (BTRF) at the University of Virginia for providing the clinical samples.