Lung cancer in never-smoker Asian females is driven by oncogenic mutations, most often involving EGFR

// Sang Yun Ha 1, * , So-Jung Choi 2, * , Jong Ho Cho 3, * , Hye Joo Choi 2 , Jinseon Lee 2 , Kyungsoo Jung 4 , Darry Irwin 5 , Xiao Liu 6, 7 , Maruja E. Lira 8 , Mao Mao 9 , Hong Kwan Kim 3 , Yong Soo Choi 3 , Young Mog Shim 3 , Woong Yang Park 10 , Yoon-La Choi 1, 4, 10 , Jhingook Kim 2, 3 1 Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 3 Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea 4 Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine, Seoul, Korea 5 Agena Bioscience, Sequenom, San Diego, CA, USA 6 BGI-Shenzhen, Shenzhen, China 7 Department of Biology, University of Copenhagen, Copenhagen, Denmark 8 Oncoloy Research Unit, Pfizer Worldwide Research and Development, San Diego, CA, USA 9 WuXi AppTec, Shanghai, China 10 Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea * These authors contributed equally to this work Correspondence to: Jhingook Kim, e-mail: jhingookkim@gmail.com Yoon-La Choi, e-mail: ylachoi@skku.edu Keywords: non-small cell lung cancer, adenocarcinoma, never-smoker female, driver mutation, EGFR Received: August 07, 2014      Accepted: December 16, 2014      Published: March 09, 2015 ABSTRACT The aim of this study was to determine the distribution of known oncogenic driver mutations in female never-smoker Asian patients with lung adenocarcinoma. We analyzed 214 mutations across 26 lung cancer-associated genes and three fusion genes using the MassARRAY® LungCarta Panel and the ALK, ROS1 , and RET fusion assays in 198 consecutively resected lung adenocarcinomas from never-smoker females at a single institution. EGFR mutation, which was the most frequent driver gene mutation, was detected in 124 (63%) cases. Mutation of ALK, KRAS, PIK3CA, ERBB2, BRAF, ROS1, and RET genesoccurred in 7% , 4%, 2.5%, 1.5%, 1%, 1%, and 1% of cases, respectively. Thus, 79% of lung adenocarcinomas from never-smoker females harbored well-known oncogenic mutations. Mucinous adenocarcinomas tended to have a lower frequency of known driver gene mutations than other histologic subtypes. EGFR mutation was associated with older age and a predominantly acinar pattern, while ALK rearrangement was associated with younger age and a predominantly solid pattern. Lung cancer in never-smoker Asian females is a distinct entity, with the majority of these cancers developing from oncogenic mutations.