Oncotarget

Clinical Research Papers:

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

Sang Yun Ha _, So-Jung Choi, Jong Ho Cho, Hye Joo Choi, Jinseon Lee, Kyungsoo Jung, Darry Irwin, Xiao Liu, Maruja E. Lira, Mao Mao, Hong Kwan Kim, Yong Soo Choi, Young Mog Shim, Woong Yang Park, Yoon-La Choi and Jhingook Kim

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Oncotarget. 2015; 6:5465-5474. https://doi.org/10.18632/oncotarget.2925

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Abstract

Sang Yun Ha1,*, So-Jung Choi2,*, Jong Ho Cho3,*, Hye Joo Choi2, Jinseon Lee2, Kyungsoo Jung4, Darry Irwin5, Xiao Liu6,7, Maruja E. Lira8, Mao Mao9, Hong Kwan Kim3, Yong Soo Choi3, Young Mog Shim3, Woong Yang Park10, Yoon-La Choi1,4,10, Jhingook Kim2,3

1Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

2Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

3Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea

4Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine, Seoul, Korea

5Agena Bioscience, Sequenom, San Diego, CA, USA

6BGI-Shenzhen, Shenzhen, China

7Department of Biology, University of Copenhagen, Copenhagen, Denmark

8Oncoloy Research Unit, Pfizer Worldwide Research and Development, San Diego, CA, USA

9WuXi AppTec, Shanghai, China

10Samsung 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.


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