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.
Highlights
Chromosomal translocations that lead to gene fusions are well-known cancer-causing genetic events that are actively used in clinical cancer diagnosis, and their gene products have been shown to be effective targets for directed therapy [1,2,3]
DUS4L-BCAP29 is widely expressed in non-neoplastic human tissues and cell lines
PAX3FOXO1 resulting from the t(2;13)(q35;q14) translocation [26] is detected in 55% of alveolar rhabdomyosarcoma (ARMS) [27], and it is used as a diagnostic aid in many pathology laboratories worldwide [28]
Summary
Chromosomal translocations that lead to gene fusions are well-known cancer-causing genetic events that are actively used in clinical cancer diagnosis, and their gene products have been shown to be effective targets for directed therapy [1,2,3]. Prominent examples include BCR-ABL in chronic myelogenous leukemia [4] with the development of Gleevec as a paradigm for targeted therapy [5], frequent gene fusion TMPRSS2-ERG in prostate cancer [6], and the rapid targeting of ALK gene fusion products with crizotinib after the discovery of EML4-ALK in lung cancer [7, 8]. Others and we have shown that fusion transcripts can be detected in normal human cell lines [9] and tissues [10,11,12,13,14,15,16,17] They may be products of intergenic splicing instead of traditional chromosomal rearrangement [18,19,20]. DUS4L-BCAP29, was found in six different tissues
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