title: High Discrepancy of Driver Mutations in Patients with NSCLC and Synchronous Multiple Lung Ground-Glass Nodules.
abstract: BACKGROUND
  The aim of this study was to investigate the discordance rates of eight known driver mutations among multiple matched intrapulmonary ground-glass nodules (GGNs) in non-small-cell lung cancer (NSCLC) patients.
  
  
  METHODS
  Tumors from 35 patients with multiple lesions resected, including confirmed NSCLC and at least one GGN, were analyzed for mutations in EGFR, KRAS, HER2, BRAF, and PIK3CA together with fusions in ALK, ROS1, and RET.
  
  
  RESULTS
  From 35 patients, a total of 72 lesions (60 were GGNs) were analyzed. These included nine adenocarcinoma in situ, nine minimal invasive adenocarcinoma, and 54 invasive adenocarcinoma. Among them, 33 tumor lesions (45.8 %) were found harboring EGFR mutations: 13 tumors with exon 19 deletion, 18 with L858R on exon 21, and two with both exon 19 del and L858R mutation. There were 5 tumors (6.9 %) harboring EML4-ALK fusion, four HER2 mutations (5.6%), three KRAS mutations (4.2%), one ROS1 fusion and one BRAF mutation. When we used the matched tumors to determine the intertumor discrepancy, only six out of 30 patients harbored identical mutations. The discordance rate of driver mutations was 80% (24 of 30) in those patients harboring at least one of the detected driver mutations. The median disease-free survival was 41.2 months (95% confidence interval: 35.8-52.6 months) and the median overall survival was "still not reached" in this cohort.
  
  
  CONCLUSIONS
  We found a high discrepancy of driver mutations among NSCLC patients with GGNs and a favorable prognosis after multiple lesions resection, which support surgical resection in this situation as a reasonable approach.
authors: Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R.China.
authors: Chunyan
authors: C
authors: Wu
authors: Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R.China.
authors: Chao
authors: C
authors: Zhao
authors: Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R.China.
authors: Yang
authors: Y
authors: Yang
authors: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R.China.
authors: Yayi
authors: Y
authors: He
authors: Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R.China.
authors: Likun
authors: L
authors: Hou
authors: Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R.China.
authors: Xuefei
authors: X
authors: Li
authors: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R.China.
authors: Guanghui
authors: G
authors: Gao
authors: Department of Imaging, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R.China.
authors: Jingyun
authors: J
authors: Shi
authors: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R.China. Electronic address: harry_ren@126.com.
authors: Shengxiang
authors: S
authors: Ren
authors: Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R.China. Electronic address: chu_haiqing@126.com.
authors: Haiqing
authors: H
authors: Chu
authors: Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R.China.
authors: Caicun
authors: C
authors: Zhou
authors: Department of Hematology & Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA.
authors: Jun
authors: J
authors: Zhang
authors: Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany.
authors: Gerald
authors: G
authors: Schmid-Bindert
mesh_terms: D065311:Adenocarcinoma in Situ / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D058534:Class I Phosphatidylinositol 3-Kinases; D018572:Disease-Free Survival; D005091:Exons; D005260:Female; D018773:Genes, erbB-1 / Q000235:genetics; D018734:Genes, erbB-2 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D055613:Multiple Pulmonary Nodules / Q000000981:diagnostic imaging / Q000235:genetics* / Q000601:surgery; D009154:Mutation; D009361:Neoplasm Invasiveness; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000601:surgery; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D011859:Radiography; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D015996:Survival Rate
chemical_list: C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C491743:MET protein, human; D011505:Protein-Tyrosine Kinases; D019859:Proto-Oncogene Proteins c-met; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C062333:ROS1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D048493:Proto-Oncogene Proteins B-raf