title: Prevalence, clinicopathologic characteristics, and molecular associations of EGFR exon 20 insertion mutations in East Asian patients with lung adenocarcinoma.
abstract: OBJECTIVE
  To define the prevalence, clinicopathologic characteristics and molecular associations of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in East Asian lung adenocarcinoma patients.
  
  
  METHODS
  A total of 1,086 lung adenocarcinomas were sequenced for EGFR mutations. EGFR and HER2 copy number variations; total and phosphorylated (p) protein expression of ErbB family members including EGFR, HER2, and HER3; phosphorylated protein expression of downstream signaling molecules including Akt and Erk; and clinicopathologic features in lung adenocarcinomas with EGFR exon 20 insertion mutations were all investigated.
  
  
  RESULTS
  EGFR exon 20 insertion mutations were present in 2.9 % of lung adenocarcinomas and 4.7 % of all the EGFR mutations. Compared to those with classic activating EGFR mutations, lung adenocarcinomas with exon 20 insertion mutations were characterized by significantly younger age at diagnosis (P = 0.032 for exon 20 insertions vs. L858R) and shorter relapse-free survival [P = 0.045 for exon 20 insertions versus (vs) exon 19 deletions]. Molecularly, samples harboring exon 20 insertion mutations had lower expression of phosphorylated (p)-EGFR (P < 0.001) and HER3 (P = 0.016). In addition, higher expression of p-Akt (P = 0.007) and lower expression of p-Erk (P = 0.009) were observed in tumors with exon 20 insertion mutations.
  
  
  CONCLUSIONS
  Lung adenocarcinomas with EGFR exon 20 insertion mutations were present in a substantial proportion. This subset showed distinct clinicopathologic features, less dependence on EGFR molecularly, and different pathway activation patterns compared to those with classic EGFR activating mutations.
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Yunjian
authors.initials: Y
authors.lastname: Pan
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Haichuan
authors.initials: H
authors.lastname: Hu
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Ting
authors.initials: T
authors.lastname: Ye
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Luo
authors.forename: Yiliang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Deng
authors.initials: D
authors.lastname: Cai
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.forename: Yihua
authors.initials: Y
authors.lastname: Sun
authors.forename: Haiquan
authors.initials: H
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D000368:Aged; D044466:Asian People / Q000235:genetics*; D002681:China; D056915:DNA Copy Number Variations; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics; D020893:Receptor, ErbB-3 / Q000032:analysis / Q000235:genetics
chemical_list: D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human