title: Mutation analysis of the EGFR gene and its downstream signaling pathway in thymic carcinoma patients from a Chinese Han population.
abstract: BACKGROUND
  For thymic carcinoma (TC), which is a rare epithelial neoplasm of the thymus gland, median survival with current treatments is only 2 years.
  
  
  OBJECTIVE
  Mutations in the epidermal growth factor receptor (EGFR) gene or its downstream effectors may cause constitutive activation that leads to cell proliferation and metastases. Thus, molecular profiling is essential for selecting TC patients who may respond to anti-EGFR therapies.
  
  
  METHODS
  Genomic DNA was extracted from 61 histological samples of TCs. Real-time polymerase chain reaction (PCR) and direct sequencing were used to assess the mutations in the EGFR downstream pathway.
  
  
  RESULTS
  Gene mutations were identified in seven patients (11.5%). In particular, the identified mutations included four mutations in the KRAS gene, one mutation in the BRAF gene, one mutation in the PIK3CA gene, and only one mutation in the EGFR gene itself. Gene mutations in the EGFR downstream pathway were associated with shorter survival time and were observed to be an independent prognostic factor for TC patients.
  
  
  CONCLUSIONS
  Mutations in the EGFR downstream pathway are not rare in TCs. These data offer interesting possibilities for the future management of TCs, particularly in the era of new targeted therapies.
authors.affiliation: Department of Respiratory Medicine, Nanjing Chest Hospital, School of Medicine, Southeast University, Nanjing, 210029, China.|Clinical Center of Nanjing Respiratory Diseases and Imaging, Nanjing, 210029, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhan
authors.affiliation: Department of Pathology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Central Laboratory, Nanjing Chest Hospital, School of Medicine, Southeast University, Nanjing, 210029, China.
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Wu
authors.affiliation: Department of Respiratory Medicine, Nanjing Chest Hospital, School of Medicine, Southeast University, Nanjing, 210029, China.|Clinical Center of Nanjing Respiratory Diseases and Imaging, Nanjing, 210029, China.
authors.forename: Zhi-Bo
authors.initials: ZB
authors.lastname: Hou
authors.affiliation: Department of Respiratory Medicine, Nanjing Chest Hospital, School of Medicine, Southeast University, Nanjing, 210029, China.|Clinical Center of Nanjing Respiratory Diseases and Imaging, Nanjing, 210029, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Qian
authors.affiliation: Department of Respiratory Medicine, Nanjing Chest Hospital, School of Medicine, Southeast University, Nanjing, 210029, China.|Clinical Center of Nanjing Respiratory Diseases and Imaging, Nanjing, 210029, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Nanjing Chest Hospital, School of Medicine, Southeast University, Nanjing, 210029, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Pathology, Nanjing Chest Hospital, School of Medicine, Southeast University, Nanjing, 210029, China.
authors.forename: Yuan-Qing
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Nanjing Chest Hospital, School of Medicine, Southeast University, Nanjing, 210029, China.
authors.forename: Ming-Yue
authors.initials: MY
authors.lastname: Wan
authors.affiliation: Department of Pathology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Nanjing Chest Hospital, School of Medicine, Southeast University, Nanjing, 210029, China.|Clinical Center of Nanjing Respiratory Diseases and Imaging, Nanjing, 210029, China.
authors.forename: Li-Ke
authors.initials: LK
authors.lastname: Yu
authors.affiliation: Department of Respiratory Medicine, Nanjing Chest Hospital, School of Medicine, Southeast University, Nanjing, 210029, China.|Clinical Center of Nanjing Respiratory Diseases and Imaging, Nanjing, 210029, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Xie
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D015536:Down-Regulation; D066246:ErbB Receptors / Q000235:genetics*; D005202:Asia, Eastern; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D018570:Risk Assessment; D015398:Signal Transduction / Q000235:genetics; D016019:Survival Analysis; D013945:Thymoma / Q000208:ethnology* / Q000235:genetics* / Q000401:mortality; D013953:Thymus Neoplasms / Q000208:ethnology* / Q000235:genetics* / Q000401:mortality
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: BRAF; EGFR; KRAS; PIK3CA; mutation analysis; thymic carcinoma