title: Lung cancer in never-smoker Asian females is driven by oncogenic mutations, most often involving EGFR.
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.
authors.affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sang Yun
authors.initials: SY
authors.lastname: Ha
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: So-Jung
authors.initials: SJ
authors.lastname: Choi
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hye Joo
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jinseon
authors.initials: J
authors.lastname: Lee
authors.affiliation: Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyungsoo
authors.initials: K
authors.lastname: Jung
authors.affiliation: Agena Bioscience, Sequenom, San Diego, CA, USA.
authors.forename: Darry
authors.initials: D
authors.lastname: Irwin
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Oncoloy Research Unit, Pfizer Worldwide Research and Development, San Diego, CA, USA.
authors.forename: Maruja E
authors.initials: ME
authors.lastname: Lira
authors.affiliation: WuXi AppTec, Shanghai, China.
authors.forename: Mao
authors.initials: M
authors.lastname: Mao
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hong Kwan
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yong Soo
authors.initials: YS
authors.lastname: Choi
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young Mog
authors.initials: YM
authors.lastname: Shim
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Woong Yang
authors.initials: WY
authors.lastname: Park
authors.affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.|Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jhingook
authors.initials: J
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D009857:Oncogenes / Q000235:genetics*; D011379:Prognosis; D012907:Smoking / Q000235:genetics*
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; adenocarcinoma; driver mutation; never-smoker female; non-small cell lung cancer