title: Response to Crizotinib Observed in Lung Adenocarcinoma with MET Copy Number Gain but without a High-Level MET/CEP7 Ratio, MET Overexpression, or Exon 14 Splicing Mutations.
abstract: MMNG HOS Transforming gene (MET) is an important driver gene in non-small cell lung cancer. Yet, MET-relevant biomarkers predictive of clinical response to MET inhibitors remain elusive. Limited studies have indicated some possibly effective biomarkers, including amplification with a high-level MET/centromere probe of chromosome 7 (CEP7) ratio, MET exon 14 (METex14) splicing mutations, and MET overexpression. MET copy number gain (MCNG) is an independent negative prognostic factor in non-small cell lung cancer. Therefore, there remains a lack of clinical evidence regarding whether MCNG is a biomarker predictive of response to MET inhibitors. Here we report a patient with lung adenocarcinoma with MCNG but without a high-level MET/CEP7 ratio or METex14 splicing mutations who achieved a rapid response to crizotinib, indicating that MCNG may be an independent predictive biomarker for response to MET inhibitors.
authors.affiliation: Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: WeiYa
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Sonography, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China. Electronic address: hmj107@163.com.
authors.forename: MeiJuan
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: You
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017398:Alternative Splicing; D002503:Centromere; D002897:Chromosomes, Human, Pair 7; D000077547:Crizotinib; D056915:DNA Copy Number Variations; D005091:Exons; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: Copy number gain; Crizotinib; Lung cancer; MET/CEP7 ratio; Mesenchymal-epithelial transition