title: MET exon 14 skipping defines a unique molecular class of non-small cell lung cancer.
abstract: OBJECTIVE
  Recurrent MET exon 14 splicing has been revealed in lung cancers and is a promising therapeutic target. Because we have limited knowledge about the natural history of MET mutant tumors, the current study was aiming to determine the clinical and pathological characteristics in non-small cell lung cancers (NSCLC).
  
  
  RESULTS
  Twenty-three patients (1.3%) were positive for MET exon 14 skipping. Patients with MET exon 14 skipping displayed unique characteristics: female, non-smokers, earlier pathology stage and older age. MET exon 14 skipping indicated an early event as other drivers in lung cancer, while MET copy number gain was more likely a late event in lung cancer. Overall survival (OS) of patients harboring MET exon 14 skipping was longer than patients with KRAS mutation. Almost four-fifths of the lung tumors with MET exon 14 skipping had EGFR and/or HER2 gene copy number gains. EGFR inhibitor showed moderate antitumor activity in treatment of a patient harboring MET exon 14 skipping.
  
  
  METHODS
  From October 2007 to June 2013, we screened 1770 patients with NSCLC and correlated MET status with clinical pathologic characteristics and mutations in EGFR, KRAS, BRAF, HER2, and ALK. Quantitative Real-Time PCR was used to detect MET gene copy number gain. Immunohistochemistry (IHC) was also performed to screen MET exon 14 skipping. Clinicopathological characteristics and survival information were analyzed.
  
  
  CONCLUSIONS
  MET exon 14 skipping was detected in 1.3% (23/1770) of the Chinese patients with NSCLC. MET exon 14 skipping defined a new molecular subset of NSCLC with identifiable clinical characteristics. The therapeutic EGFR inhibitors might be an alternative treatment for patients with MET mutant NSCLC.
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Difan
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Ye
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Cancer Research Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Su
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Massachusetts General Hospital Cancer Center, Boston, MA, USA.
authors.forename: Haichuan
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Xuxia
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Ji
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Haiquan
authors.initials: H
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D002681:China; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*
chemical_list: D020033:Protein Isoforms; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: MET; non-small cell lung cancer; surgery; targeted therapy