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YunYu Lin,1,* Yan Lei,2,* LinWei Li,2 Xiaoxing Su,2 Qiqi Tian,1 Wendy Wu2 1Respiratory Medicine, NingHai First Hospital, NingBo, 315600, People’s Republic of China; 2Berry Oncology Institutes, Berry Oncology Corporation, Fuzhou, 350200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiqi Tian; Wendy Wu, Email 252446462@qq.com; wujy3261@berryoncology.comObjective: Previous studies have shown that fusion partners have a potential role in influencing different tumorigenic abilities of ROS1 fusion variants, as well as potential differential responses to crizotinib. Therefore, it is important to accurately identify the type of ROS1 rearrangement in NSCLC for clinical treatment selection.Materials and Methods: Deep-coverage targeting solid tumor 31 cancer-related genes panel was used to capture DNA-based NGS information to detect gene fusion. RNA fusion panel based on hybrid capture sequencing was performed to verify gene fusions from total RNA which isolated from formalin fixed paraffin-embedded (FFPE) tissue blocks.Results: Using DNA-targeted NGS method, we identified a novel BAIAP2-ROS1 fusion in a 71-year-old non-smoking female patient with stage IVB lung adenocarcinoma. Rearrangement consisted of BAIAP2 in exon1-exon13 of chr17: q23 and ROS1 in exon35-exon43 of chr6: q22, which were further confirmed by RNA-based NGS methodology. A complete kinase domain in ROS1 fusion was preserved. The patient subsequently received crizotinib and showed significant tumor reduction until 17 months, who got benefit from targeted therapy.Conclusion: This study discovered a novel BAIAP2-ROS1 rearrangement; it provides more knowledge of ROS1 fusion in clinical personalized treatment. The good response to crizotinib therapy emphasizes the importance of DNA-based and RNA-based NGS in rare fusion identification in clinical practice.Keywords: BAIAP2-ROS1 fusion, advanced lung adenocarcinoma, sensitive to crizotinib, next-generation sequencing