Frequency of MET exon 14 skipping mutations in non-small cell lung cancer according to technical approach in routine diagnosis: results from a real-life cohort of 2,369 patients

Oncogenic alterations occurring in non-small cell lung cancer (NSCLC) are attractive because they may confer sensitivity to targeted therapies and help personalise medicine with the use of targeted therapy (1). Alterations of the gene coding for the mesenchymal epithelial transition receptor (MET), a tyrosine kinase receptor, have been reported in NSCLC, including copy number variations (polysomy and amplification) and mutational activating variants (2,3). According to the Cancer Genome Atlas, the latter occur in 7% of pulmonary adenocarcinoma (2) with different frequencies according to ethnicity (4,5). The most frequent mutations are MET exon 14 skipping mutations that activate MET through reduction of MET degradation and increased MET activity (6,7). Because of the highly diverse sequence composition of MET exon 14 skipping mutations, the frequency of these mutations is strongly dependent on the technique used to detect MET alterations. It varies from 3% of pulmonary adenocarcinoma using direct sequencing or hybrid capture new generation sequencing (7,8) to 4.3% using whole-exome sequencing (2)