Identification of a novel WNK1–ROS1 fusion in a lung adenocarcinoma sensitive to crizotinib

Abstract Objectives Non-small-cell lung cancer (NSCLC) has various driver mechanisms, including ROS1 rearrangement with different fusion patterns. There is a need to identify and evaluate new ROS1 fusions and the response to targeted therapy. Materials and methods A targeted next-generation sequencing (NGS) panel was used to analyze DNA extracted from tumor tissue and blood samples from an NSCLC patient. Results were validated using Sanger sequencing. Results We found a novel ROS1 rearrangement form, namely a WNK1–ROS1 fusion. The transmembrane and kinase domains of ROS1 remained intact in this fusion. No EGFR , MET , KRAS , ALK , ROS1 or other NSCLC driver mutations were detected in the patient. The patient achieved a partial response after treatment with crizotinib. When disease progressed, ROS1 G2032R mutation—a classical mechanism of crizotinib resistance—was detected in the DNA sample extracted from the patient’s plasma sample. Conclusion We identified a novel WNK1–ROS1 fusion that was sensitive to crizotinib and developed an ROS1 G2032R mutation when the disease progressed. The WNK1–ROS1 rearrangement appeared to be a novel driver of the lung cancer.