Next Generation Sequencing Reveals a Synchronous Trilateral Lung Adenocarcinoma Case with Distinct Driver Alterations of EGFR 19 Deletion or EGFR 20 Insertion or EZR-ROS1 Fusion

Xuhui Zhang,1,* Jiemei Feng,2,* Xiaoxing Su,3 Yan Lei,3 Wendy Wu,3 Xiangyang Cheng4 1Department of Oncology, Guangdong Second Provincial General Hospital, Guangzhou, People’s Republic of China; 2Department of Respiratory and ICU, Guigang People’s Hospital, Guigang, 537100, People’s Republic of China; 3Clinical Research Division, Berry Oncology Corporation, Fuzhou, 350200, People’s Republic of China; 4Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wendy Wu; Xiangyang Cheng Email wujy3261@berryoncology.com xuewu1901@sina.comObjective: Synchronous multiple primary lung cancer (SMPLC) has a reported occurrence from 0.5% to 2% in lung cancer, and the surgical treatment and prognosis were quite diverse. With the discovery of driver mutations in lung adenocarcinoma (ADC), next-generation sequencing (NGS) would provide an explicit answer to the key question, whether individual tumors represent intrapulmonary metastases or independent tumors. Here, we reported a 64-year-old female diagnosed with a synchronous trilateral early-stage ADC with distinct driver alterations.Materials and Methods: NGS test targeting 31 cancer-relevant genes and amplification RNA sequencing (if gene fusion was found on DNA level) were performed on the surgical tumor tissue.Results: A 64-year-old Chinese female never smoker was found with one nodule in the right upper lobe and two nodules in the right middle lobe through chest computed tomography. The lesions were resected through video-assisted thoracic surgery and diagnosed with stage IA ADC, T1N0M0, in the postoperative pathology. NGS detected three independent driver mutations in three primary sites, respectively, EGFR 19del, EGFR 20ins and ROS1 fusion.Conclusion: This is the first report of a synchronous trilateral early-stage ADC with distinct driver alterations. All individual tumors were independent identified by NGS methodology, which had provided a clear answer to the key question of SMPLC in this case and should be used as a routine genetic test to explore fully pathological diagnosis and more comprehensive oncogenesis information in the early-stage ADC clinical prevention.Keywords: synchronous multiple primary lung cancer, lung adenocarcinoma, NGS, EGFR mutation, ROS1 fusion