Identification of gene fusion transcripts by transcriptome sequencing in BRCA1-mutated breast cancers and cell lines

RNA sequencing was performed on ten breast cancer transcriptomes (five BRCA1-mutated breast cancer cell lines, three BRCA1-mutated primary tumours, two secretory breast cancer primary tumours and one non-tumorigenic breast epithelial cell line) using the Illumina Genome Analyzer. We sought to identify putative gene fusions using a bioinformatics approach. As a proof of concept, we were able to identify two previously characterized gene fusions in our samples using both single-end and paired-end approaches. In addition, we identified three novel in-frame fusions, but none were recurrent. Two of the candidates, WWC1-ADRBK2 in HCC3153 cell line and ADNP-C20orf132 in a primary tumour, were confirmed by Sanger sequencing and RT-PCR. RNA-Seq expression profiling of these two fusions showed a distinct overexpression of the 3' partner genes, suggesting that its expression may be under the control of the 5' partner gene's regulatory elements.