ROS1-ADGRG6: a case report of a novel ROS1 oncogenic fusion variant in lung adenocarcinoma and the response to crizotinib

ROS1 rearrangements are validated drivers in lung cancer, which have been identified in a small subset (1–2%) of patients with non-small cell lung cancer (NSCLC). To date, 18 fusion genes of ROS1 have been identified in NSCLC. The ALK inhibitor (crizotinib) exhibits therapeutic effect against ROS1-rearranged NSCLC. Next-generation sequencing (NGS) technology represents a novel tool for ROS1 detection that covers many fusion genes. A 55-year-old female with EGFR mutation (L858R) was diagnosed with lung adenocarcinoma, who was responsive to first-generation EGFR-tyrosine kinase inhibitor (TKI). Afterwards, she developed acquired resistance accompanied with a ROS1 rearrangement. A NGS assay showed that the tumor had a novel ROS1-ADGRG6 rearrangement generated by the fusion of exons of 1–33 of ROS1 on chr6: q22.1 to exons of 2–26 of ADGRG6 on chr6: q24.2. The patient was obviously responsive to crizotinib. We firstly identified ROS1-ADGRG6 fusion variant in NSCLC by NGS, which should be considered in further ROS1 detecting assays.