Use of clinical RNA-sequencing in the detection of actionable fusions compared to DNA-sequencing alone.
3077 Background: While targeted DNA-seq can detect clinically actionable fusions in tumor tissue samples, technical and analytical challenges may give rise to false negatives. RNA-based, whole-exome sequencing provides a complementary method for fusion detection, and may improve the identification of actionable variants. In this study, we quantify this benefit using a large, real-world clinical dataset to assess actionable fusions detected from RNA in conjunction with DNA profiling. Methods: Using the Tempus Research Database, we retrospectively analyzed a de-identified dataset of ̃80K samples (77.4K patients) profiled with the Tempus xT assay (both DNA-seq with fusion detection in 21 genes and whole exome capture RNA-seq). Only patients that had successful RNA- and DNA-seq were included. Fusions were detected using the Tempus bioinformatic and clinical workflow. Candidate fusions were filtered based on read support thresholds, fusion annotation (i.e., breakpoints, reading frame, conse