Chien-Hung Gow1, Min-Shu Hsieh2, Shang-Gin Wu3, Jin-Yuan Shih4. 1. 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. 2. Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan. 3. 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. 4. 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.
Abstract
INTRODUCTION: 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. 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 METΔ14 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 METΔ14 mutation. We analysed the demographic data and clinical outcomes of METΔ14 mutation positive lung cancer patients and compared them to those of METΔ14 mutation negative lung cancer patients. RESULTS: In total, 27 lung adenocarcinoma (ADC) patients and 1 squamous cell carcinoma patient with the METΔ14 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 METΔ14 mutation exhibited a strong cytoplasmic expression of MET. METΔ14 mutation positive patients were generally quite elderly individuals. Stage IV METΔ14 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 METΔ14 mutation positive lung cancer patients is comparable to that of the major driver gene mutation negative lung cancer patients.
INTRODUCTION: 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 cancerpatients have yet to be determined. METHODS: A one-step reverse transcription-polymerase chain reaction (RT-PCR), using RNA samples from 850 East Asian lung cancerpatients, was performed in order to detect METΔ14 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 METΔ14 mutation. We analysed the demographic data and clinical outcomes of METΔ14 mutation positive lung cancerpatients and compared them to those of METΔ14 mutation negative lung cancerpatients. RESULTS: In total, 27 lung adenocarcinoma (ADC) patients and 1 squamous cell carcinomapatient with the METΔ14 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 cancerpatients harboring a METΔ14 mutation exhibited a strong cytoplasmic expression of MET. METΔ14 mutation positive patients were generally quite elderly individuals. Stage IV METΔ14 mutation positive lung cancerpatients 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 cancerpatients without appropriate tyrosine kinase inhibitors treatment. CONCLUSIONS: The OS of METΔ14 mutation positive lung cancerpatients is comparable to that of the major driver gene mutation negative lung cancerpatients.
Authors: S Betty Yan; Suzane L Um; Victoria L Peek; Jennifer R Stephens; Wei Zeng; Bruce W Konicek; Ling Liu; Jason R Manro; Volker Wacheck; Richard A Walgren Journal: Invest New Drugs Date: 2017-11-29 Impact factor: 3.850