title: Response and acquired resistance to crizotinib in Chinese patients with lung adenocarcinomas harboring MET Exon 14 splicing alternations.
abstract: Approximately 10% of lung adenocarcinomas harbor aberrations that are targetable using the approved multitargeted TKI crizotinib. MET exon 14 skipping mutation predicts for response to crizotinib in human lung adenocarcinomas. However, a substantial part of patients still has no sufficient tissue to perform genomic analysis. As a promising noninvasive biomarker and potential surrogate for the entire tumor genome, circulating tumor DNA (ctDNA) has been applied to the detection of driver gene mutations. Here we described the MET exon 14 splicing mutations in cell-free circulating-tumor DNA by next-generation sequencing (NGS) technology. Patient firstly responded to crizotinib therapy within four months, however, three acquired mutation in the MET kinase domain, D1228N/H and Y1230H, were found at the time of disease progression. To our knowledge, this is the first clinical report of three mutations simultaneously arising in a patient with MET exon 14 splicing mutation.
authors.affiliation: Department of Oncology, Changzhou Tumor Hospital Soochow University, Changzhou 213001, China.
authors.forename: Hua-Jie
authors.initials: HJ
authors.lastname: Dong
authors.affiliation: Department of Oncology, Changzhou Tumor Hospital Soochow University, Changzhou 213001, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Oncology, Changzhou Tumor Hospital Soochow University, Changzhou 213001, China.
authors.forename: Chang-Ling
authors.initials: CL
authors.lastname: Wu
authors.affiliation: Department of Oncology, Changzhou Tumor Hospital Soochow University, Changzhou 213001, China.
authors.forename: Xiao-Yue
authors.initials: XY
authors.lastname: Zhou
authors.affiliation: Department of Oncology, Changzhou Tumor Hospital Soochow University, Changzhou 213001, China.
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Lu
authors.affiliation: Department of Oncology, Changzhou Tumor Hospital Soochow University, Changzhou 213001, China. Electronic address: zhoutong2930@163.com.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D017398:Alternative Splicing; D000970:Antineoplastic Agents / Q000627:therapeutic use; D044466:Asian People; D000074141:Circulating Tumor DNA / Q000235:genetics; D000077547:Crizotinib; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005091:Exons; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D015898:Tomography Scanners, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000074141:Circulating Tumor DNA; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: Acquired resistance; Circulating tumor DNA; Lung cancer; MET exon 14 splicing mutations