title: A comprehensive analysis of clinical outcomes in lung cancer patients harboring a MET exon 14 skipping mutation compared to other driver mutations in an East Asian population.
abstract: Recurrent somatic splice-site alterations at MET exon 14 (METΔ14), which result in exon skipping and MET proto-oncogene, receptor tyrosine kinase (MET) activation, have been characterised. However, their demographic features and clinical outcomes in East Asian lung cancer patients have yet to be determined.
  
  
  
  A one-step reverse transcription-polymerase chain reaction (RT-PCR), using RNA samples from 850 East Asian lung cancer patients, was performed in order to detect METΔ14and five other major driver mutations, including those in the EGFR, KRAS, ALK, HER2, and ROS1 genes. Immunohistochemistry (IHC) was used to confirm the overexpression of MET in patients harbouring the METΔ14mutation. We analysed the demographic data and clinical outcomes of METΔ14mutation positive lung cancer patients and compared them to those of METΔ14mutation negative lung cancer patients.
  
  
  
  In total, 27 lung adenocarcinoma (ADC) patients and 1 squamous cell carcinoma patient with the METΔ14mutation were identified. The overall incidence was 3.3% for lung cancer and 4.0% for lung ADC. IHC demonstrated that the majority of lung cancer patients harboring a METΔ14mutation exhibited a strong cytoplasmic expression of MET. METΔ14mutation positive patients were generally quite elderly individuals. Stage IV METΔ14mutation positive lung cancer patients receiving no specific anti-MET therapy were observed to have a similar overall survival (OS) compared to patients in the all negative group (P>0.05). In the multivariate analysis, mutation status was found not to be a major risk factor for OS in lung cancer patients without appropriate tyrosine kinase inhibitors treatment.
  
  
  
  The OS of METΔ14mutation positive lung cancer patients is comparable to that of the major driver gene mutation negative lung cancer patients.
authors.affiliation: Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; Department of Healthcare Information and Management, Ming-Chuan University, Taiwan; Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Gow
authors.affiliation: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Min-Shu
authors.initials: MS
authors.lastname: Hsieh
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital Yun-Lin, Branch, Yun-Lin, Taiwan; Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Shang-Gin
authors.initials: SG
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: jyshih@ntu.edu.tw.
authors.forename: Jin-Yuan
authors.initials: JY
authors.lastname: Shih
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D044466:Asian People / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005091:Exons; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013624:Taiwan / Q000453:epidemiology
chemical_list: D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019859:Proto-Oncogene Proteins c-met; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C117307:KRAS protein, human; C000715470:MAS1 protein, human; C000626173:ALK protein, human; C508053:ERBB2 protein, human; C062333:ROS1 protein, human
keywords: Driver mutation; Lung cancer; MET exon 14 skipping; One-step reverse transcriptase-polymerase chain reaction; Overall survival