Detection of actionable structural variants in advanced non-small cell lung cancer with RNA-NGS plus DNA-NGS

The NCCN guidelines for non-small cell lung cancer suggest that adding RNA next-generation sequencing (NGS) may improve the detection of actionable fusions and splicing variants (aSVs) compared with DNA-NGS alone. However, in current routine clinical care there is limited adoption of RNA-NGS. A multicenter, retrospective cohort study included patients with advanced non-small cell lung cancer with sufficient tissue sample quantities for both RNA-NGS and DNA-NGS testing. In this cohort study of 5570 patients, 8.8% had at least 1 aSV detected by 1 or both assays. Concurrent RNA-NGS and DNA-NGS testing identified 15.3% more patients harboring an aSV compared with DNA-NGS alone, including 14.3% more patients with actionable fusions and 18.6% more patients with MET exon 14 skipping alterations. The authors conclude that these results suggest that concurrent RNA-NGS and DNA-NGS testing should be used clinically to maximize sVA detection.