{"entity":{"id":"met-ex14","kind":"biomarker","name":"MET exon 14 skipping mutation","aka":["METex14","MET exon 14 skipping","MET ex14","METΔex14","MET exon 14 alteration","MET splice site mutation"],"tldr":"MET exon 14 skipping is a splice-site change that lets the MET receptor escape degradation and keep signalling. It is found in 3 to 4 percent of lung cancers and is treated with capmatinib or tepotinib.","summary":"Mutations at the exon 14 splice acceptor or donor sites, or in the Y1003 juxtamembrane region, cause the exon to be skipped, removing the CBL binding site. They are detected by DNA sequencing (with splice-site coverage) or, more sensitively, RNA sequencing of tissue or plasma. Capmatinib (Tabrecta, 2020) is labelled for metastatic NSCLC with a mutation that leads to MET exon 14 skipping as detected by an FDA-approved test, and tepotinib (Tepmetko, 2021) for NSCLC harbouring MET exon 14 skipping alterations; FoundationOne CDx and Liquid CDx are the companion diagnostics for both.","asOf":"2026-09-23","links":[{"label":"TABRECTA prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=455892c3-d144-4ba8-9ab4-79cabff9876d"},{"label":"TEPMETKO prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=80a0f1b9-071a-47f5-9e67-32d638a669dc"}],"tags":["biomarker","met"],"related":["met-amplification-readout","met-overexpression"],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["capmatinib","tepotinib","capmatinib-tepotinib","foundationone-cdx"],"companies":[],"institutions":[],"pathways":[],"terms":["met-exon-14-skipping","ngs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-awad-met-exon-14-mutations-lung-jco-2016","paper-frampton-met-exon-14-cancer-discov-2015","paper-tcga-lung-adenocarcinoma-nature-2014","paper-lindeman-lung-molecular-testing-guideline-jto-2018"],"journals":[],"dependsOn":[],"notes":["Lung cancer: 2 to 4% of adenocarcinomas, 3.0% of 933 non-squamous cancers in the founding clinical series and 4% read directly in messenger RNA in the TCGA cohort (Awad 2016, Cancer Genome Atlas Research Network 2014). The variants are splice-site and juxtamembrane alterations in the introns flanking exon 14, so a coding-exon panel returns a wild-type result; detection needs intron baiting or RNA. The patients are older (median 72.5 years), 68% women and 36% never smokers, and stage IV cases carry concurrent MET amplification and strong c-Met staining far more often than early-stage ones (Awad 2016)."],"target":"met","measurement":"sequencing-variant","scoringRule":{"text":"A single nucleotide variant or indel at the MET exon 14 splice sites or within exon 14 that leads to exon 14 skipping, by DNA or RNA sequencing of tissue or plasma.","quote":"MET single nucleotide variants and indels that lead to MET exon 14 skipping","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools","sourceLabel":"FDA: List of FDA-Authorized Companion Diagnostic Devices"},"thresholds":[{"value":"MET exon 14 skipping","drugId":"capmatinib","cancerId":"nsclc","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=455892c3-d144-4ba8-9ab4-79cabff9876d","quote":"TABRECTA is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test.","status":"current"},{"value":"MET exon 14 skipping","drugId":"tepotinib","cancerId":"nsclc","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=80a0f1b9-071a-47f5-9e67-32d638a669dc","quote":"TEPMETKO is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition ( MET ) exon 14 skipping alterations.","status":"current"}],"tests":["foundationone-cdx","foundationone-liquid-cdx","guardant360-cdx","tempus-xt","trusight-oncology-comprehensive","caris-mi-profile"],"assays":["foundationone-cdx-panel","foundationone-liquid-cdx"],"companionDiagnostics":[{"device":"FoundationOne CDx","maker":"Foundation Medicine","companyId":"foundation-medicine","drugs":["capmatinib"],"indication":"Non-Small Cell Lung Cancer (NSCLC) - Tissue","pma":"P170019/S011 (05/06/2020)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"FoundationOne Liquid CDx","maker":"Foundation Medicine","companyId":"foundation-medicine","drugs":["capmatinib"],"indication":"Non-Small Cell Lung Cancer (NSCLC) - Plasma","pma":"P190032/S001 (07/15/2021)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"FoundationOne CDx","maker":"Foundation Medicine","companyId":"foundation-medicine","drugs":["tepotinib"],"indication":"Non-small cell lung cancer (NSCLC) - Tissue","pma":"P170019/S067 (05/12/2026)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"}],"forPatient":"A MET exon 14 skipping result means capmatinib or tepotinib, both tablets, are on label for advanced lung cancer. These tumours are common in older patients and respond less well to immunotherapy alone, so the MET tablet is usually chosen first or after one line of chemotherapy."},"route":"/biomarkers/met-ex14/","neighbours":{"biomarker":[{"id":"met-overexpression","kind":"biomarker","name":"c-Met protein overexpression (IHC 3+ in >= 50% of tumour cells)","route":"/biomarkers/met-overexpression/"},{"id":"met-amplification-readout","kind":"biomarker","name":"MET amplification (gene copy number)","route":"/biomarkers/met-amplification-readout/"}],"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"drug":[{"id":"capmatinib","kind":"drug","name":"Capmatinib","route":"/drugs/capmatinib/"},{"id":"capmatinib-tepotinib","kind":"drug","name":"Capmatinib & tepotinib","route":"/drugs/capmatinib-tepotinib/"},{"id":"foundationone-cdx","kind":"drug","name":"FoundationOne CDx / Liquid CDx","route":"/drugs/foundationone-cdx/"},{"id":"tepotinib","kind":"drug","name":"Tepotinib","route":"/drugs/tepotinib/"}],"term":[{"id":"met-exon-14-skipping","kind":"term","name":"MET exon 14 skipping mutation","route":"/terms/met-exon-14-skipping/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"}],"paper":[{"id":"paper-tcga-lung-adenocarcinoma-nature-2014","kind":"paper","name":"Comprehensive molecular profiling of lung adenocarcinoma","route":"/key-papers/paper-tcga-lung-adenocarcinoma-nature-2014/"},{"id":"paper-awad-met-exon-14-mutations-lung-jco-2016","kind":"paper","name":"MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression","route":"/key-papers/paper-awad-met-exon-14-mutations-lung-jco-2016/"},{"id":"paper-frampton-met-exon-14-cancer-discov-2015","kind":"paper","name":"MET exon 14 splicing alterations across tumour types and their sensitivity to MET inhibitors","route":"/key-papers/paper-frampton-met-exon-14-cancer-discov-2015/"},{"id":"paper-lindeman-lung-molecular-testing-guideline-jto-2018","kind":"paper","name":"Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors","route":"/key-papers/paper-lindeman-lung-molecular-testing-guideline-jto-2018/"}],"target":[{"id":"met","kind":"target","name":"MET","route":"/targets/met/"}]}}