title: Identification of five driver gene mutations in patients with treatment-naïve lung adenocarcinoma in Taiwan.
abstract: BACKGROUND
  It is important to select appropriate targeted therapies for subgroups of patients with lung adenocarcinoma who have specific gene alterations.
  
  
  METHODS
  This prospective study was a multicenter project conducted in Taiwan for assessment of lung adenocarcinoma genetic tests. Five oncogenic drivers, including EGFR, KRAS, BRAF, HER2 and EML4-ALK fusion mutations, were tested. EGFR, KRAS, BRAF and HER2 mutations were assessed by MALDI-TOF MS (Cohort 1). EML4-ALK translocation was tested by Ventana method in EGFR-wild type patients (Cohort 2).
  
  
  RESULTS
  From August 2011 to November 2013, a total of 1772 patients with lung adenocarcinoma were enrolled. In Cohort 1 analysis, EGFR, KRAS, HER2 and BRAF mutations were identified in 987 (55.7%), 93 (5.2%), 36 (2.0%) and 12 (0.7%) patients, respectively. Most of these mutations were mutually exclusive, except for co-mutations in seven patients (3 with EGFR + KRAS, 3 with EGFR + HER2 and 1 with KRAS + BRAF). In Cohort 2 analysis, 29 of 295 EGFR-wild type patients (9.8%) were positive for EML4-ALK translocation. EGFR mutations were more common in female patients and non-smokers and KRAS mutations were more common in male patients and smokers. Gender and smoking status were not correlated significantly with HER2, BRAF and EML4-ALK mutations. EML4-ALK translocation was more common in patients with younger age.
  
  
  CONCLUSIONS
  This was the first study in Taiwan to explore the incidence of five oncogenic drivers in patients with lung adenocarcinoma and the results could be valuable for physicians in consideration of targeted therapy and inclusion of clinical trials.
authors: Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
authors: Kuo-Hsuan
authors: KH
authors: Hsu
authors: Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Chao-Chi
authors: CC
authors: Ho
authors: Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; Department of Respiratory Therapy, China Medical University, Taichung, Taiwan.
authors: Te-Chun
authors: TC
authors: Hsia
authors: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors: Jeng-Sen
authors: JS
authors: Tseng
authors: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors: Kang-Yi
authors: KY
authors: Su
authors: Divisions of Medical Oncology and Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors: Ming-Fang
authors: MF
authors: Wu
authors: Division of Chest Medicine, Department of Internal Medicine, Taichung Tzu-Chi Hospital, Taichung, Taiwan; School of Post-baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan.
authors: Kuo-Liang
authors: KL
authors: Chiu
authors: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Tsung-Ying
authors: TY
authors: Yang
authors: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors: Kun-Chieh
authors: KC
authors: Chen
authors: Department of Critical Care Medicine, Taichung Tzu-Chi Hospital, Taichung, Taiwan; Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors: Hean
authors: H
authors: Ooi
authors: School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Pulmonary Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors: Tzu-Chin
authors: TC
authors: Wu
authors: Department of Respiratory Therapy, China Medical University, Taichung, Taiwan; Division of Pulmonary and Critical Care Medicine, China Medical University Hospital, Taichung, Taiwan.
authors: Hung-Jen
authors: HJ
authors: Chen
authors: Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
authors: Hsuan-Yu
authors: HY
authors: Chen
authors: Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
authors: Chi-Sheng
authors: CS
authors: Chang
authors: Division of Thoracic Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Chung-Ping
authors: CP
authors: Hsu
authors: Division of Thoracic Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
authors: Jiun-Yi
authors: JY
authors: Hsia
authors: Division of Thoracic Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
authors: Cheng-Yen
authors: CY
authors: Chuang
authors: Division of Thoracic Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
authors: Chin-Hung
authors: CH
authors: Lin
authors: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
authors: Jeremy J W
authors: JJ
authors: Chen
authors: Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Kuan-Yu
authors: KY
authors: Chen
authors: Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Wei-Yu
authors: WY
authors: Liao
authors: Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Jin-Yuan
authors: JY
authors: Shih
authors: Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Sung-Liang
authors: SL
authors: Yu
authors: Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Chong-Jen
authors: CJ
authors: Yu
authors: Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Pan-Chyr
authors: PC
authors: Yang
authors: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Gee-Chen
authors: GC
authors: Chang
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D015331:Cohort Studies; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012907:Smoking; D013624:Taiwan / Q000453:epidemiology; D018631:ras Proteins / Q000235:genetics
chemical_list: D066246:ErbB Receptors; D015514:Oncogene Proteins, Fusion; D048493:Proto-Oncogene Proteins B-raf; D018719:Erb-b2 Receptor Tyrosine Kinases; D018631:ras Proteins; C522504:EML4-ALK fusion protein, human; C508053:ERBB2 protein, human; C482119:BRAF protein, human