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• W2891801100 abstract "IntroductionGenomic alterations affecting splice sites of MNNG HOS transforming gene (MET) exon 14 were recently identified in NSCLC patients. Objective responses to MET tyrosine kinase inhibitors have been reported in these patients. Thus, detection of MET exon 14 splice site mutations represents a major challenge. So far, most of these alterations were found by full-exome sequencing or large capture-based next-generation sequencing (NGS) panels, which are not suitable for routine diagnosis.MethodsAiming to provide a molecular testing method applicable in routine practice, we first developed a fragment-length analysis for detecting deletions in introns flanking MET exon 14. Second, we designed an optimized targeted NGS panel called CLAPv1, covering the MET exon 14 and flanking regions in addition to the main molecular targets usually covered in genomic testing. In patients with MET exon 14 mutations, MET gene amplification, gene copy number and MET receptor expression were also determined.ResultsAmong 1514 formalin-fixed paraffin-embedded NSCLC samples, nonoptimized NGS allowed detection of MET exon 14 mutations in only 0.3% of the patients, and fragment length analysis detected deletions in 1.1% of the patients. Combined, the optimized CLAPv1 panel and fragment-length analysis implemented for routine molecular testing revealed MET exon 14 alterations in 2.2% of 365 additional NSCLC patients. MET gene amplification or high gene copy number was observed in 6 of 30 patients (20%) harboring MET exon 14 mutations.ConclusionsThese results show that optimized targeted NGS and fragment-length analysis improve detection of MET alterations in routine practice." @default.
• W2891801100 created "2018-09-27" @default.
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• W2891801100 date "2018-12-01" @default.
• W2891801100 modified "2023-10-16" @default.
• W2891801100 title "Optimization of Routine Testing for MET Exon 14 Splice Site Mutations in NSCLC Patients" @default.
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• W2891801100 doi "https://doi.org/10.1016/j.jtho.2018.08.2023" @default.
• W2891801100 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30195702" @default.
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