Analysis of ROS1 fusions in nonlung solid tumors.

Abstract

e15124 Background: Somatic chromosomal fusions involving ROS1 produce chimeric proteins that drive tumorigenesis and progression. Currently, ROS1-directed tyrosine kinase inhibitors (TKIs) are effective treatments for advanced non-small cell lung cancer (NSCLC) patients (pts) with ROS1 fusions. Except for NSCLC, Glioblastoma and spitzoid neoplasms, ROS1 fusions have been rarely reported in other cancers. Therefore, clarifying the patterns and frequency of ROS1 fusions in multi-cancer may help pts benefit from ROS1 inhibit therapy. Methods: To characterize the ROS1-fusion patterns in Chinese pts, we retrospectively analyzed the next-generation sequencing (NGS) data of 11,740 pts from 2017 to 2021. Results: In this study, a total of 12 ROS1 fusions were identified in this Chinese nonlung solid tumors cohort (12/11,740). Among them, the ROS1-fusion positive rate is 0.037% in colonrectal cancer pts (2/5,467), 0.13% in stomach cancer pts (3/2,268), 0.11% in liver cancer pts (2/1,774), 0.19% in kidney cancer pts (1/540), 0.21% in pancreatic cancer pts (2/966) and 0.28% in sarcoma pts (2/725). Particularly, we observed the coexistence of CD80- ROS1 and Intergenic- ROS1 in the same kidney cancer pt. Among ROS1 fusions described in this cohort, the frequency of known partners was 16.67%, and the frequency of unreported partners was 83.33%. Compared with NSCLC (1%̃2%), the ROS1 fusions are less frequent in the nonlung solid tumors (≤0.3%), and fusion partners are mostly unreported, which means that the efficacy of ROS1 TKIs in these solid tumor pts may be different from that in lung cancer. Therefore, more attention and in-depth research are needed in ROS1 fusion positive nonlung solid tumors, which have a low incidence and few cases, so as to bring clinical benefits to more pts. Conclusions: Through NGS, we identified ROS1 fusion patterns in non-lung solid tumors, most of which fusion partners are unreported, expanding the range of ROS1 fusions documented in tumors and providing potential for ROS1 TKIs in multiple tumors.[Table: see text]