title: RET fusions define a unique molecular and clinicopathologic subtype of non-small-cell lung cancer.
abstract: OBJECTIVE
  The RET fusion gene has been recently described in a subset of non-small-cell lung cancers (NSCLCs). Because we have limited knowledge about these tumors, this study was aimed at determining the clinicopathologic characteristics of patients with NSCLC harboring the RET fusion gene.
  
  
  METHODS
  We examined the RET fusion gene in 936 patients with surgically resected NSCLC using a reverse transcriptase polymerase chain reaction (PCR) plus quantitative real-time PCR strategy, with validation using immunohistochemical and fluorescent in situ hybridization assays. A subset of 633 lung adenocarcinomas was also studied for EGFR, KRAS, HER2, and BRAF mutations, as well as ALK rearrangements. Patient characteristics, including age, sex, smoking history, stage, grade, International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of subtypes of lung adenocarcinoma, and relapse-free survival, were collected.
  
  
  RESULTS
  Of 936 patients with NSCLC, the RET fusion gene was exclusively detected in 13 patients (11 of 633 patients with adenocarcinomas and two of 24 patients with adenosquamous cell carcinomas). Of the 13 patients, nine patients had KIF5B-RET, three patients had CCDC6-RET, and one patient had a novel NCOA4-RET fusion. Patients with lung adenocarcinomas with RET fusion gene had more poorly differentiated tumors (63.6%; P = .029 for RET v ALK, P = .007 for RET v EGFR), with a tendency to be younger (≤ 60 years; 72.7%) and never-smokers (81.8%) and to have solid subtype (63.6%) and a smaller tumor (≤ 3 cm) with N2 disease (54.4%). The median relapse-free survival was 20.9 months.
  
  
  CONCLUSIONS
  RET fusion occurs in 1.4% of NSCLCs and 1.7% of lung adenocarcinomas and has identifiable clinicopathologic characteristics, warranting further clinical consideration and targeted therapy investigation.
authors.affiliation: Fudan University Shanghai Cancer Center, Shanghai, China 200032.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Haichuan
authors.initials: H
authors.lastname: Hu
authors.forename: Yunjian
authors.initials: Y
authors.lastname: Pan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Ting
authors.initials: T
authors.lastname: Ye
authors.forename: Chenguang
authors.initials: C
authors.lastname: Li
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Luo
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Yongming
authors.initials: Y
authors.lastname: Lu
authors.forename: Qiong
authors.initials: Q
authors.lastname: Lu
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: David
authors.initials: D
authors.lastname: Garfield
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.forename: Hongbin
authors.initials: H
authors.lastname: Ji
authors.forename: William
authors.initials: W
authors.lastname: Pao
authors.forename: Yihua
authors.initials: Y
authors.lastname: Sun
authors.forename: Haiquan
authors.initials: H
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D005260:Female; D050939:Gene Fusion; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*
chemical_list: D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human