iFUSE: integrated fusion gene explorer.

UNLABELLED: We present iFUSE (integrated fusion gene explorer), an online visualization tool that provides a fast and informative view of structural variation data and prioritizes those breaks likely representing fusion genes. This application uses calculated break points to determine fusion genes based on the latest annotation for genomic sequence information, and where relevant the structural variation (SV) events are annotated with predicted RNA and protein sequences. iFUSE takes as input a Complete Genomics (CG) junction file, a FusionMap fusion detection report file or a file already analysed and annotated by the iFUSE application on a previous occasion. RESULTS: We demonstrate the use of iFUSE with case studies from tumour-normal SV detection derived from Complete Genomics whole-genome sequencing results. AVAILABILITY: iFUSE is available as a web service at http://ifuse.erasmusmc.nl.

Gene fusions by chromothripsis of chromosome 5q in the VCaP prostate cancer cell line.

The VCaP cell line is widely used in prostate cancer research as it is a unique model to study castrate resistant disease expressing high levels of the wild type androgen receptor and the TMPRSS2-ERG fusion transcript. Using next generation sequencing, we assembled the structural variations in VCaP genomic DNA and observed a massive number of genomic rearrangements along the q arm of chromosome 5, characteristic of chromothripsis. Chromothripsis is a recently recognized phenomenon characterized by extensive chromosomal shattering in a single catastrophic event, mainly detected in cancer cells. Various structural events identified on chromosome 5q of VCaP resulted in gene fusions. Out of the 18 gene fusion candidates tested, 15 were confirmed on genomic level. In our set of gene fusions, only rarely we observe microhomology flanking the breakpoints. On RNA level, only five transcripts were detected and NDUFAF2-MAST4 was the only resulting in an in-frame fusion transcript. Our data indicate that although a marker of genomic instability, chromothripsis might lead to only a limited number of functionally relevant fusion genes.