Identification of a Novel RBPMS-ROS1 Fusion in an Adolescent Patient with Microsatellite-Instable Advanced Lung Adenocarcinoma Sensitive to Crizotinib: A Case Report

Abstract Introduction Human c-ros oncogene 1 (ROS1) rearrangement is a distinctive molecular subtype identified in 1-2% of non-small-cell lung cancer (NSCLC) tumors. Since the first gene rearrangement involving the ROS1 gene was described in 2003, multiple ROS1 fusion partner genes have been reported. Crizotinib, a multi-targeted MET/ALK/ROS1 tyrosine kinase inhibitor approved by the FDA, shows efficacy in the treatment of NSCLC patients with common ROS1 fusions. However, its efficacy in patients with rare ROS1 fusions remains unknown. Case presentation Here, we report a 16-year-old boy diagnosed with advanced lung adenocarcinoma. Paired tumor-normal next-generation sequencing was performed on DNA derived from pericardial effusion and peripheral blood with simultaneous analyses of genetic alterations, microsatellite instability (MSI), and tumor mutation burden (TMB). A total of 34 somatic variations, including a novel RBPMS-ROS1 (Exon 1:Exon 32) fusion, were identified. In addition, the sample was found to exhibit MSI-H and TMB-H. The patient was administered crizotinib and showed a rapid, favorable response in both intracranial and primary lung lesions. Conclusion This case supports the use of crizotinib in NSCLC patients with RBPMS-ROS1 rearrangement. Broader molecular profiling is strongly recommended for patients with NSCLC to identify novel actionable fusions.