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

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 103; pp. 82 - 89
• Main Authors: Gow, Chien-Hung, Hsieh, Min-Shu, Wu, Shang-Gin, Shih, Jin-Yuan
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.01.2017
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Adult; Aged; Aged, 80 and over; Anaplastic Lymphoma Kinase; Asian Continental Ancestry Group - genetics; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Disease-Free Survival; Driver mutation; ErbB Receptors - genetics; Exons; Female; Hematology, Oncology and Palliative Medicine; Humans; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; MET exon 14 skipping; Middle Aged; Mutation; Oncogene Proteins, Fusion - genetics; One-step reverse transcriptase-polymerase chain reaction; Overall survival; Protein Kinase Inhibitors - therapeutic use; Protein-Tyrosine Kinases - genetics; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-met - genetics; Proto-Oncogene Proteins c-met - metabolism; Proto-Oncogene Proteins p21(ras) - genetics; Pulmonary/Respiratory; Receptor Protein-Tyrosine Kinases; Receptor, ErbB-2 - genetics; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction - methods; Taiwan - epidemiology; Taiwan; ADC; Driver mutation; SCC; One-step reverse transcriptase-polymerase chain reaction; OS; IHC; Lung cancer; MET exon 14 skipping; Overall survival; MET; METΔ14; MET proto-oncogene, receptor tyrosine kinase; adenocarcinoma; MET Δ14; overall survival; immunohistochemistry; squamous cell carcinoma
• DOI: 10.1016/j.lungcan.2016.12.001
• ISSN: 0169-5002

•We detected METΔ14 and five other major driver mutations in lung cancer patients.•METΔ14 mutation can be successfully detected in a one-step RT-PCR using RNA samples.•METΔ14 mutation positive samples exhibited a strong cytoplasmic expression of MET.•Stage IV METΔ14 positive and driver mutation negative groups have a similar OS.•Mutation status was not a major risk factor for OS in advanced lung cancer. 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 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. 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. The OS of METΔ14 mutation positive lung cancer patients is comparable to that of the major driver gene mutation negative lung cancer patients.