RNA Sequencing and Tissue Strategies for ROS1 Detection

Julia K. Rotow, MD, explains how RNA-based next-generation sequencing (NGS) fits into testing for newly diagnosed advanced nonsquamous non-small cell lung cancer (NSCLC) in a discussion moderated by Matthew A. Gubens, MD, MS, with panelists Estelamari Rodriguez, MD, MPH, and Ana I. Velázquez Mañana, MD, MSc. Dr. Rotow notes that DNA-based NGS long served as the standard and often the only test, although it can miss fusions, including ROS1 fusions. She says RNA-based profiling after negative DNA testing uncovers actionable drivers in a sizable fraction of patients, particularly those with low tumor mutational burden or no tobacco use history, and urges clinicians to confirm that their platform covers both DNA and RNA. When tissue is scant, Dr. Rotow considers a negative liquid biopsy nondiagnostic rather than negative because liquid assays can struggle to detect fusions. She favors early coordination on tissue adequacy and repeat biopsy when needed, pushing hardest for young patients and those with no tobacco use history.