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Background  Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and a highly heterogeneous disease with a diversity of phenotypes and genotypes in different populations. The purpose of this study is to investigate oncogenic alterations of lung adenocarcinoma (LUAD) in eastern China and their significance in targeted therapies.    Methods  This study enrolled 101 LUAD patients and used a customized DNA panel to detect molecular alterations. Comprehensive analysis of mutations and clinical application of genomic profiling was carried out.    Results  The most commonly mutated genes were epidermal growth factor receptor ( EGFR ) (53%) and tumor protein p53 ( TP53 ) (32%). The less frequently mutated genes were erb-b2 receptor tyrosine kinase 2 ( ERBB2 ) (25%), ATR serine/threonine kinase ( ATR ) (20%), CCAAT enhancer binding protein alpha ( CEBPA ) (16%), RB transcriptional corepressor 1 ( RB1 ) (16%), transcription factor 7 like 2 ( TCF7L2 ) (14%), ROS proto-oncogene 1, receptor tyrosine kinase ( ROS1 ) (12%) and spectrin alpha, erythrocytic 1 ( SPTA1 ) (12%). Among them, the frequency of  ERBB2 ,  ATR ,  CEBPA ,  RB1  and  TCF7L2  mutations was much higher than that in the databases. Seventy percent of the patients harbored at least one actionable alteration according to the OncoKB evidence.  CEBPA  mutations affected the efficacy of  EGFR -tyrosine kinase inhibitors.  ERBB2 ,  CEBPA  and  TCF7L2  mutated tumors tend to have higher tumor mutation burden (TMB).    Conclusions  LUAD patients from eastern China have a unique profile of mutations. The targeted DNA panel is helpful for personalized treatment decision of LUAD patients, and specific mutations may affect the efficacy of targeted therapies.

Genetic Alteration Profiling of Chinese Lung Adenocarcinoma and Its Effect on Targeted Therapy Efficacy