{"entity":{"id":"met-exon-14-skipping","kind":"term","name":"MET exon 14 skipping mutation","aka":["MET exon 14","METex14","MET ex14","MET exon 14 skipping","MET splice-site mutation","METex14 skipping alteration","c-Met immunohistochemistry","c-Met IHC","MET overexpression","MET copy number","MET-altered"],"tldr":"A splice-site mutation that makes cells skip exon 14 of the MET gene removes the receptor's off switch, so MET piles up on the cell surface; found in about 3 percent of lung adenocarcinomas, typically in older smokers or never-smokers, it is targeted by the pills capmatinib, tepotinib and savolitinib.","summary":"What is measured: a mutation at the splice sites flanking exon 14 of MET that deletes the juxtamembrane domain containing the Y1003 degradation signal. How: RNA-based next-generation sequencing is preferred because it detects the skipped transcript directly; DNA panels must cover the intronic splice regions and still miss 10 to 20 percent because the breakpoints vary; plasma cell-free DNA can detect it. Related tests: FISH or sequencing copy number for MET amplification (high-level gain, a MET to CEP7 ratio of 5 or more or ten copies or more, is more likely to respond) and c-Met immunohistochemistry for overexpression (3+ in half or more of cells selects telisotuzumab vedotin, not the kinase inhibitors). Frequency: 3 to 4 percent of non-small-cell lung cancers, 20 to 30 percent of pulmonary sarcomatoid carcinomas, and papillary renal cell carcinoma. What a positive result changes: capmatinib (GEOMETRY mono-1, response rate 68 percent first line), tepotinib (VISION) or savolitinib (China; and with osimertinib for MET-amplified resistance in EGFR-mutant disease) replace chemotherapy and immunotherapy, which works poorly here despite high PD-L1; resistance comes through MET D1228 and Y1230 mutations or KRAS and other bypass lesions; telisotuzumab vedotin serves c-Met-overexpressing EGFR wild-type nonsquamous disease. Where it matters: MET-altered NSCLC, NSCLC and papillary RCC.","asOf":"2026-09-17","links":[],"tags":[],"related":["met","met-amplification","capmatinib","tepotinib","savolitinib","crizotinib","telisotuzumab-vedotin","rna-seq","gatekeeper-mutation"],"cancers":["met-altered-nsclc","nsclc","papillary-rcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},"route":"/terms/met-exon-14-skipping/","neighbours":{"target":[{"id":"met","kind":"target","name":"MET","route":"/targets/met/"}],"term":[{"id":"met-amplification","kind":"term","name":"MET amplification (bypass resistance)","route":"/terms/met-amplification/"},{"id":"gatekeeper-mutation","kind":"term","name":"On-target resistance mutations (gatekeeper, solvent-front, compound)","route":"/terms/gatekeeper-mutation/"}],"drug":[{"id":"capmatinib","kind":"drug","name":"Capmatinib","route":"/drugs/capmatinib/"},{"id":"crizotinib","kind":"drug","name":"Crizotinib","route":"/drugs/crizotinib/"},{"id":"savolitinib","kind":"drug","name":"Savolitinib","route":"/drugs/savolitinib/"},{"id":"telisotuzumab-vedotin","kind":"drug","name":"Telisotuzumab vedotin","route":"/drugs/telisotuzumab-vedotin/"},{"id":"tepotinib","kind":"drug","name":"Tepotinib","route":"/drugs/tepotinib/"}],"technology":[{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"}],"cancer":[{"id":"met-altered-nsclc","kind":"cancer","name":"MET exon 14 and MET-amplified non-small-cell lung cancer","route":"/cancers/met-altered-nsclc/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"papillary-rcc","kind":"cancer","name":"Papillary renal cell carcinoma","route":"/cancers/papillary-rcc/"}]}}