Breakpoint analysis of transcriptional and genomic profiles uncovers novel gene fusions spanning multiple human cancer types (RNA-seq)
We report the design and implementation of a "breakpoint analysis" pipeline to discover novel gene fusions by tell-tale transcript level or genomic DNA copy number transitions occurring within genes.  We use this method to prioritize candidate rearrangements from high density array CGH datasets as well as exon-resolution expression microarrays.  We mine both publicly available data as well as datasets generated in our laboratory.  Several gene fusion candidates were chosen for further characterization, and corresponding samples were profiled using paired end RNA sequencing to discover the identity of the gene fusion.  Using this approach, we report the discovery and characterization of novel gene fusions spanning multiple cancer subtypes including angiosarcoma, pancreatic cancer, anaplastic astrocytoma, melanoma, breast cancer, and T-cell acute lymphoblastic leukemia.  Taken together, this study provides a robust approach for gene fusion discovery, and our results highlight a more widespread role of fusion genes in cancer pathogenesis. Overall design: Breakpoint analysis for the discovery of novel gene fusions across human cancers