Recurrent fusion RNA DUS4L-BCAP29 in non-cancer human tissues and cells

Abstract

Traditional gene fusions are involved in the development of various neoplasia. DUS4L-BCAP29, a chimeric fusion RNA, has been reported to be a cancer-fusion in prostate and gastric cancer, in addition to playing a tumorigenic role. Here, we showed that the DUS4L-BCAP29 fusion transcript exists in a variety of normal tissues. It is also present in non-cancer epithelial, as well as in fibroblast cell lines. Quantitatively, the fusion transcript has a comparable expression in non-cancerous, gastric and prostate cell lines and tissues as in the cancer cell lines and tissues. The loss-of-function approach as previously reported is not sufficient to prove the functionality of the fusion. On the other hand, the gain-of-function approach showed that overexpression of DUS4L-BCAP29 promotes cell growth and motility, even in non-cancer cells. 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 that its pro-growth effect is not unique to cancer cells.