Abstract
Abstract The fusion RNA, SLC45A3-ELK4, was found to be a product of cis-splicing between the two adjacent genes (cis-SAGe). Previously, we used LNCaP, a prostate cancer cell line as a model, and identified 16 additional cis-SAGe events by silencing transcription factor CTCF and paired-end RNA sequencing. One out of the 16 fusion RNAs, D2HGDH-GAL3ST2, is more frequently seen in cancer samples, and seems to be enriched in the African American group. It is more frequently detected in late stage cancer, suggesting a role in cancer progression. By studying the features associated with the 16 fusions, we developed a set of rules: 1) the parental genes are same-strand-neighboring genes, 2) the distance of between the genes is within 30kb; 3) the 5' genes are actively transcribing; and 4) the fusion RNAs tend to have the second-to-last exon in the 5' genes joined to the second exon in the 3' genes. To investigate the cis-SAGe fusion RNAs at global, we first randomly selected 20 neighboring genes in the genome, and detected four fusion events using these rules in prostate cancer and non-cancerous cells. To further understand the cis-SAGe fusions in human tissues and cells, we then performed, curated and analyzed nearly 300 RNA-seq libraries covering 30 different non-neoplastic human tissues and cells. More than 10,000 fusion transcripts were found. We focused on the neighboring fusions and performed analysis. Appling our cis-SAGe rules, we identified around 1486 cis-SAGe fusion candidates. A few sequence motifs were found enriched close to the fusion junction sites. We performed functional experiments on a few widely expressed fusions, such as ADCK4-NUMBL, CLN6-CAML4, DUS4L-BCAP29, and found that silencing them resulted in dramatic reduction in moral cell growth and /or motility. Citation Format: Fujun Qin. Landscape of fusion RNAs generated by cis-spliced adjacent genes in cancer and normal physiology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1476.
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