Chromosomal translocations that create fusion genes are commonly found in cancer and drive an estimated 20% of all cases. Current diagnostic techniques are only capable of detecting single fusion events, and false-negative results are a leading cause of misdiagnosis. We have developed two new universal gene fusion assays, based on RNA Capture Sequencing.

We designed two sets of capture array probes targeting genes involved in fusion events in blood cancer (BCFuse) and solid tumours (STFuse). We performed RNA Capture Sequencing using established cell lines and patient material with well-characterised gene fusions. Sequencing data was assessed to determine assay efficacy, gene fusion status and prevalence, and prognostic gene expression levels.

Both gene fusion assays successfully identified the known chromosomal translocation events in the samples. Gene fusions were also identified from FFPE cancer biopsies. Sensitivity of the BCFuse capture was determined at 1:10,000 cells, and proved capable of resolving clonal cell populations in samples. In addition, the STFuse capture provided a molecular diagnosis for two prostate cancer patients previously classified as “TMPRSS2—ERG negative” using standard diagnostics. These candidates represent a rare ETV1 gene fusion and a novel ERG fusion.

The impact of a fusion event is dependent on the gene partners involved and diagnosing the precise nature of the fusion can impact on disease stratification and prognosis. We have generated two universal tests capable of assessing all currently known cancer fusion genes, and with the potential to resolve novel fusions and alternative fusion isoforms. Following assessment in larger patient cohorts, we believe that these tests will be usefully applied as clinical diagnostics.