A novel ros1-fbxl17 fusion co-existing with cd74-ros1 fusion may improve sensitivity to crizotinib and prolong progression-free survival of patients with lung adenocarcinoma

Abstract

Purpose: The rearrangement of ROS1 (C-ros oncogene 1) is an important driver of non-small cell lung cancer (NSCLC). Currently, only approximately 24 ROS1 fusion partners have been shown to be sensitive to crizotinib. Although fusion partner determination is not required to treat patients with tyrosine kinase inhibitor, the correlation between ROS1 phenotypes and efficacies still needs more researches. Furthermore, non-reciprocal/reciprocal ROS1 translocations are rare and have not yet been reported. Thus, more novel ROS1 fusion partners and non-reciprocal/reciprocal fusions need to be provided and supplemented to guide targeted therapy and prognosis for patients. Case Presentation: Targeted next-generation sequencing panel was used to identify ROS1 rearrangements in a Chinese patient with advanced lung adenocarcinoma. We identified a non-reciprocal/reciprocal ROS1 translocation which contained a novel ROS1-FBXL17 (F-box and leucine-rich repeat protein 17) fusion co-existing with the CD74-ROS1 fusion and the patient was sensitive to crizotinib. The ROS1 rearrangement was then validated using RT-qPCR. The progression-free survival (PFS) was 15.7 months which exceeded the highest PFS level (14.2 months) in the Chinese population reported recently. Thus, this non-reciprocal/reciprocal ROS1 translocation patient had an excellent efficacy to crizotinib which was different from that in ALK. And it may be possible that the ROS1-FBXL17 fusion in this patient synergistically promotes the sensitivity of the CD74-RSO1 fusion to crizotinib. Conclusion: The ROS1-FBXL17 fusion may be a novel driver of NSCLC and we provide a non-reciprocal/reciprocal ROS1 translocation mode very sensitive to crizotinib. Our study adds new data to the ROS1 fusion database and provides a reference strategy for the clinical treatment of patients with double ROS1 fusions or non-reciprocal/reciprocal ROS1 translocation.