MET Exon 14 Skipping Mutation in Non-Small Cell Lung Cancer Identified by Anchored Multiplex PCR and Next- Generation Sequencing.

Recurrent MET exon 14 (MET ex14) somatic splice site mutations have been described in 0.6 to 7% of lung non-small cell carcinomas (NSCLC) [1-3]. These mutations result in exon 14 skipping and subsequent MET activation with clinical trials demonstrating promising sensitivity to c-MET inhibitors [3]. These mutations are typically mutually exclusive of other lung adenocarcinoma known oncogenic driver mutations (e.g., EGFR, KRAS, BRAF, ERBB2, ALK, ROS1) but frequently co-occur with MDM2 and CDK4 amplification on chromosome 12q [2]. MET ex 14 mutations display diversity with upwards of 126 distinct DNA sequence variants described necessitating comprehensive genomic profiling by clinical laboratories for routine detection of these mutations in patients [2]. Of note, these MET ex14 splice site mutations are not limited to just NSCLC but also have been identified in a small percentage of gliomas and gastro-esophageal carcinomas [2,4]… continued in article

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