Pitfalls in Detecting MET Exon 14 Skipping Variants by DNA- and RNA-Based Next-Generation Sequencing Technologies in a Large Real-World Cohort and Results of the First Multinational External Quality Assessment Schemes

MET exon 14 skipping mutations in non–small-cell lung cancer (NSCLC) are important biomarkers for targeted therapy, making accurate detection essential. This study analyzed 379 NSCLCs with mutations in MET exon 14 and adjacent splice sites using DNA- and RNA-based next-generation sequencing (NGS). The 379 samples contained 171 distinct mutations around MET exon 14, highlighting the diversity; 114 mutations were analyzed with a DNA- and an RNA-based NGS assay. Two large deletions and one synonymous splice variant causing exon 14 skipping were only detected by RNA-based NGS.