Abstract:
Fusion genes are a major cause of cancer. Their rapid and accurate diagnosis can inform
clinical action, but current molecular diagnostic assays are restricted in resolution and
throughput. Here, we show that targeted RNA sequencing (RNAseq) can overcome these
limitations. First, we establish that fusion gene detection with targeted RNAseq is both
sensitive and quantitative by optimising laboratory and bioinformatic variables using spike-in
standards and cell lines. Next, we analyse a clinical patient cohort and improve the overall
fusion gene diagnostic rate from 63% with conventional approaches to 76% with targeted
RNAseq while demonstrating high concordance for patient samples with previous diagnoses.
Finally, we show that targeted RNAseq offers additional advantages by simultaneously
measuring gene expression levels and profiling the immune-receptor repertoire. We anticipate
that targeted RNAseq will improve clinical fusion gene detection, and its increasing use
will provide a deeper understanding of fusion gene biology.
