The implementation of an RNA-based gene fusion assay into a diagnostic oncology department: an Australian perspective

Accurate detection of oncogenic gene fusions is important for histological diagnosis of a subset of tumours. Some fusions are also the target of precision therapies. We describe our validation and early diagnostic results for the detection of fusions using the commercially available Illumina TruSight RNA Fusion Panel (TRFP) and the Arriba fusion detection algorithm. Retrospective validation showed that this assay demonstrated high accuracy (94% positive predictive agreement) for a wide variety of fusions. Prospective diagnostic data comprised a cohort of 131 clinical samples (102 mesenchymal tumours, 29 epithelial tumours), of which 80 were excisional specimens and 51 were small specimens, predominantly core biopsies. The test failure rate was 10.7%. We detected 64 (54.7%) clinically-actionable fusions in passed samples, including 12 (10.3%) that either changed or were critical for the diagnosis and 14 (12.0%) that were potentially therapeutically targetable. Most samples (89.7%) fulfilled criteria for partial reimbursement by the Australian Government Medical Benefits Scheme. In addition to describing the utility of an RNA-based fusion assay in cancer diagnostics, it is hoped that this study will provide practical advice for other laboratories considering introducing such a test.