Clinical Implications of a Targeted RNA Sequencing Panel in the Detection of Gene Fusions in Solid Tumors.

Abstract The detection of recurrent gene fusions can help confirm diagnoses in solid tumors, particularly when the morphology and staining are unusual or nonspecific, and can guide therapeutic decisions. While fluorescence in situ hybridization (FISH) and PCR are often used to identify fusions, the rearrangement must be suspected, with only a few prioritized probes run. We hypothesized that the Illumina TruSight RNA Fusion Panel, which detects fusions of 507 genes and their partners, would uncover fusions with greater sensitivity than other approaches, leading to changes in diagnosis, prognosis, or therapy. Targeted RNA sequencing was performed on formalin fixed paraffin embedded (FFPE) sarcoma and carcinoma cases in which FISH, RT-PCR, or DNA-based sequencing was conducted during the diagnostic workup. Out of 153 cases, 138 (90%) were sequenced with adequate quality control metrics. 101/138 (73%) cases were concordant by RNA sequencing and the prior test method. RNA sequencing identified an additional 30 cases (22%) with fusions that were not detected by conventional methods. In 7 cases (5%), the additional fusion information provided by RNA sequencing would have altered the diagnosis and management. 19 novel fusion pairs (not previously described in the literature) were discovered (14%). Overall, the findings show that a targeted RNA sequencing method can detect gene fusions in FFPE specimens with high sensitivity.