e21162 Background: Targeted therapy has greatly extended the survival of certain molecular selected cancer patients. However, lots of them would eventually develop drug resistance and required alternative treatment. Research on the genomic changes before and after treatment allows us to understand the mechanism of drug resistance and to develop new treatment strategies. Methods: A total of 143 patients were enrolled and their specimens were sequenced with a panel of 680 cancer-related genes in this study. Briefly, tumor FFPE samples before treatment (T1) were collected and underwent deep sequencing (2000X), and blood samples after treatment (T2) were collected, cell-free DNA (cfDNA) was isolated and sequenced (20000X). Patients with positive EGFR mutations at T1 received TKIs afterwards. Results: A total of 160 mutations were identified in T1 and 206 mutations were found in T2 samples, while 90 of them were shared in both time points. EGFR mutations were found in 95 (66.4%) patients at T1 and 101 (70.6%) patients at T2. ERBB2 mutations were found in 9 (6.3%) patients at T1 and 19 (13.3%) patients at T2. Among them, one patient had ERBB2 amplification at T1, and new ERBB2 amplifications were found in 11 patients at T2. Conclusions: ERBB2 amplifications are associated with TKI treatment, and are likely to be involved with disease progression and TKI drug resistance.