title: The Unique Characteristics of MET Exon 14 Mutation in Chinese Patients with NSCLC.
abstract: Predictive biomarkers of mesenchymal-to-epithelial transition factor (MET)-targeted therapy remain elusive. Since the discovery of the MNNG HOS Transforming gene (MET) exon 14 mutation, it has been found to have the best potential to become one precise biomarker for MET-targeted therapy. Here, we present the unique characteristics of MET exon 14 mutations in Chinese patients with NSCLC.
  
  
  
  A total of 1296 patients with NSCLC were screened for MET exon 14 mutations. Next-generation sequencing was performed on the DNA of 968 patients and Sanger sequencing was conducted on complementary DNA of the other 328 patients. Immunohistochemical analysis and fluorescence in situ hybridization were also performed on all specimens.
  
  
  
  Twelve patients had MET exon 14 mutations. These accounted for only 0.9% of adenocarcinoma. Thus, the mutations were present at less than half the frequency of their occurrence in Western patients (0.9% versus 3% in Chinese and white patients, respectively, χ(2) = 15.1, p < 0.001). Samples from six patients with MET exon 14 mutations were analyzed using immunohistochemical analysis and fluorescence in situ hybridization. We found no significant relationships among the mutation, MET amplification, and MET overexpression. In two patients who received crizotinib, only one patient (who exhibited MET amplification) experienced a partial response; the progression-free survival was 9 months. However, it remains unclear whether the sensitivity of this patient to crizotinib was conferred by the MET exon 14 mutation per se or by MET amplification. In the other patient with concomitant MET exon 14 skipping and KRAS G12D mutation, the disease progressed in only 1 month.
  
  
  
  MET exon 14 mutation per se may not be sufficiently robust for use in defining a subset of NSCLCs. Further research on MET exon 14 mutations, MET amplification, and MET overexpression is required. Maybe a panel of biomarkers will be necessary in the future.
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Si-Yang
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Lan-Ying
authors.initials: LY
authors.lastname: Gou
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: An-Na
authors.initials: AN
authors.lastname: Li
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Lou
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Hong-Fei
authors.initials: HF
authors.lastname: Gao
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Su
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Jin-Ji
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Xu-Chao
authors.initials: XC
authors.lastname: Zhang
authors.affiliation: Geneseeq Biotechnology, Inc., Nanjing, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Zhong-Yi
authors.initials: ZY
authors.lastname: Dong
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Wen-Zhao
authors.initials: WZ
authors.lastname: Zhong
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China. Electronic address: syylwu@live.cn.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D005091:Exons; D005260:Female; D005784:Gene Amplification; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*
chemical_list: C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: Biomarker; Chinese; Clinical characteristics; MET exon 14; NSCLC