Gene structure alterations, such as chromosomal rearrangements that develop fusion genes, often contribute to
tumorigenesis. It has been shown that the fusion genes identified in public
RNA-sequencing datasets are mainly derived from intrachromosomal rearrangements. In this study, we explored fusion transcripts in clinical
ovarian cancer specimens based on our
RNA-sequencing data. We successfully identified an in-frame fusion transcript SPON1-TRIM29 in chromosome 11 from a recurrent
tumor specimen of high-grade serous
carcinoma (HGSC), which was not detected in the corresponding primary
carcinoma, and validated the expression of the identical fusion transcript in another
tumor from a distinct HGSC patient.
Ovarian cancer A2780 cells stably expressing SPON1-TRIM29 exhibited an increase in cell growth, whereas a decrease in apoptosis was observed, even in the presence of anticancer drugs. The
siRNA-mediated silencing of SPON1-TRIM29 fusion transcript substantially impaired the enhanced growth of A2780 cells expressing the chimeric gene treated with anticancer drugs. Moreover, a subcutaneous xenograft model using athymic mice indicated that SPON1-TRIM29-expressing A2780 cells rapidly generated
tumors in vivo compared to control cells, whose growth was significantly repressed by the fusion-specific
siRNA administration. Overall, the SPON1-TRIM29 fusion gene could be involved in
carcinogenesis and
chemotherapy resistance in
ovarian cancer, and offers potential use as a diagnostic and therapeutic target for the disease with the fusion transcript.