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

Introduction: Recurrent somatic splice-site alterations at MET exon 14 (MET 14), 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. Methods: 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 MET Delta 14 and 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 MET Delta 14 mutation. We analysed the demographic data and clinical outcomes of MET Delta 14 mutation positive lung cancer patients and compared them to those of MET 14 mutation negative lung cancer patients. Results: In total, 27 lung adenocarcinoma (ADC) patients and 1 squamous cell carcinoma patient with the MET 14 mutation 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 MET Delta 14 mutation exhibited a strong cytoplasmic expression of MET. MET Delta 14 mutation positive patients were generally quite elderly individuals. Stage IV MET Delta 14 mutation 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. Conclusions: The OS of MET Delta 14 mutation positive lung cancer patients is comparable to that of the major driver gene mutation negative lung cancer patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.