Case Study: The Recurrent Fusion RNA DUS4L-BCAP29 in Noncancer Human Tissues and Cells

Traditional gene fusions are involved in the development of various neoplasias. DUS4L-BCAP29, a chimeric fusion RNA, has been reported to be a cancer-related fusion in prostate and gastric cancers. This chimeric RNA is believed to play a tumorigenic role. Here, we showed that the DUS4L-BCAP29 fusion transcript exists in a variety of normal tissues. It is also present in noncancerous epithelial and fibroblast cell lines. Quantitatively, the fusion transcript has a similar expression level in noncancerous gastric and prostate cell lines and tissues to its expression in cancerous cell lines and tissues. Previously, a loss-of-function approach was used to report a probable functionality for this fusion. However, this approach is not sufficient to prove such functionality. Alternatively, a gain-of-function approach showed that overexpression of DUS4L-BCAP29 promotes cell growth and motility, even in noncancerous cell lines. Finally, we provide further evidence that the fusion transcript is a product of cis-splicing between adjacent genes. In summary, we believe that in contrast to traditional gene fusions, DUS4L-BCAP29 cannot be used as a cancer biomarker. Instead, it is a fusion transcript that exists in normal physiology and its progrowth effect is not unique to cancer situations.