OncoTargets and Therapy (Nov 2020)
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
Shaowei Lan,1,2,* Hui Li,1,2,* Ying Liu,3 Jinhua Xu,3 Zhicheng Huang,4 Shi Yan,1,2 Qiang Zhang,5 Ying Cheng1– 3 1Translational Oncology Research Lab, Jilin Provincial Cancer Hospital, Changchun 130012, People’s Republic of China; 2Jilin Provincial Key Laboratory of Molecular Diagnostics for Lung Cancer, Jilin Provincial Cancer Hospital, Changchun 130012, People’s Republic of China; 3Department of Medical Thoracic Oncology, Jilin Provincial Cancer Hospital, Changchun 130012, People’s Republic of China; 4Department of Radiology, Jilin Provincial Cancer Hospital, Changchun 130012, People’s Republic of China; 5Burning Rock Biotech, Guangzhou 510000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying ChengJilin Provincial Cancer Hospital, 1066 Jinhu Road, Changchun, Jilin, People’s Republic of ChinaTel +86-431-80596051Email [email protected]: 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.Keywords: ROS1-FBXL17 fusion, CD74-ROS1 fusion, non-reciprocal/reciprocal ROS1 translocation, next-generation sequencing, intratumor heterogeneity, non-small cell lung cancer
