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.

Purpose: The rearrangement of (C-ros oncogene 1) is an important driver of non-small cell lung cancer (NSCLC). Currently, only approximately 24 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 phenotypes and efficacies still needs more researches. Furthermore, non-reciprocal/reciprocal translocations are rare and have not yet been reported. Thus, more novel 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 rearrangements in a Chinese patient with advanced lung adenocarcinoma. We identified a non-reciprocal/reciprocal translocation which contained a novel (F-box and leucine-rich repeat protein 17) fusion co-existing with the fusion and the patient was sensitive to crizotinib. The 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 translocation patient had an excellent efficacy to crizotinib which was different from that in . And it may be possible that the fusion in this patient synergistically promotes the sensitivity of the fusion to crizotinib.

Conclusion: The fusion may be a novel driver of NSCLC and we provide a non-reciprocal/reciprocal translocation mode very sensitive to crizotinib. Our study adds new data to the fusion database and provides a reference strategy for the clinical treatment of patients with double fusions or non-reciprocal/reciprocal translocation.