AUTHOR=Liu Jie , Xu Wang-yang , Ye Maosong , Liu Zilong , Li Chun 

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

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.726547

DOI=10.3389/fonc.2021.726547

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>The most commonly mutated genes were epidermal growth factor receptor (<italic>EGFR</italic>) (53%) and tumor protein p53 (<italic>TP53</italic>) (32%). The less frequently mutated genes were erb-b2 receptor tyrosine kinase 2 (<italic>ERBB2</italic>) (25%), ATR serine/threonine kinase (<italic>ATR</italic>) (20%), CCAAT enhancer binding protein alpha (<italic>CEBPA</italic>) (16%), RB transcriptional corepressor 1 (<italic>RB1</italic>) (16%), transcription factor 7 like 2 (<italic>TCF7L2</italic>) (14%), ROS proto-oncogene 1, receptor tyrosine kinase (<italic>ROS1</italic>) (12%) and spectrin alpha, erythrocytic 1 (<italic>SPTA1</italic>) (12%). Among them, the frequency of <italic>ERBB2</italic>, <italic>ATR</italic>, <italic>CEBPA</italic>, <italic>RB1</italic> and <italic>TCF7L2</italic> 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. <italic>CEBPA</italic> mutations affected the efficacy of <italic>EGFR</italic>-tyrosine kinase inhibitors. <italic>ERBB2</italic>, <italic>CEBPA</italic> and <italic>TCF7L2</italic> mutated tumors tend to have higher tumor mutation burden (TMB).</p></sec><sec><title>Conclusions</title><p>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.</p></sec>