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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.
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.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
It made MET exon 14 a clinical entity rather than a sequencing curiosity, and identified the patients most likely to be missed: older people whose age would otherwise argue against broad sequencing.
The paper established MET exon 14 skipping as a bona fide lung cancer driver and showed why RNA-based or broad DNA testing is needed to detect it, paving the way for capmatinib and tepotinib.
It is the reference table the field still argues against, and it made two practical points that outlived it: a tumour with no driver on a standard panel usually has one that the panel did not look for, and pathway activity measured on protein does not follow from the mutation list.
Shares MET exon 14 skipping mutation, Tepotinib, Capmatinib, MET amplification (bypass resistance).
Shares Tepotinib, Capmatinib, Savolitinib, Crizotinib.
Shares MET exon 14 splicing alterations across tumour types and their sensitivity to MET inhibitors, Tepotinib, Capmatinib, MET exon 14 and MET-amplified non-small-cell lung cancer.
Shares Capmatinib, MET amplification (bypass resistance), Crizotinib, MET exon 14 and MET-amplified non-small-cell lung cancer.
Shares MET exon 14 skipping mutation, 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, Telisotuzumab vedotin, MET.
Shares Telisotuzumab vedotin, MET exon 14 and MET-amplified non-small-cell lung cancer, MET, Non-small-cell lung cancer.
Shares Tepotinib, MET exon 14 and MET-amplified non-small-cell lung cancer, MET, Lung cancer (all types).
Shares Telisotuzumab vedotin, MET exon 14 and MET-amplified non-small-cell lung cancer, MET, Lung cancer (all types).