{"entity":{"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","aka":[],"tldr":"Mutations that make lung cancer cells skip a single piece of the MET gene define a group of patients who are much older than the rest of lung oncology, mostly women, and often never smokers.","summary":"Next-generation sequencing results from 6,376 cancers were interrogated for MET exon 14 mutations, and the clinical, pathological and genomic characteristics of the positive cases were compared with those of KRAS- and EGFR-mutant lung cancers. MET exon 14 mutations were identified in 28 of 933 non-squamous lung cancers, 3.0%, and in no other cancer type in the series. Patients were significantly older, median 72.5 years, than patients with EGFR-mutant (61 years) or KRAS-mutant (65 years) disease; 68% were women and 36% never smokers. Stage IV MET exon 14 tumours were significantly more likely to carry concurrent MET amplification (mean MET to chromosome 7 ratio 4.3 against 1.4) and strong c-Met immunohistochemical expression (mean H score 253 against 155) than earlier-stage cases. A patient whose tumour carried both an exon 14 mutation and amplification of the mutated allele had a major partial response to crizotinib.","asOf":"2026-09-25","links":[{"label":"Awad et al., J Clin Oncol 2016: MET exon 14 mutations across 6,376 cancers, with age, amplification and c-Met overexpression","url":"https://doi.org/10.1200/JCO.2015.63.4600"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26729443/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["cgp","histopathology-ihc"],"targets":["met","egfr","kras"],"drugs":["crizotinib","capmatinib","tepotinib"],"companies":[],"institutions":["dana-farber"],"pathways":["rtk-activation"],"terms":["met-exon-14-skipping","met-amplification","gene-amplification","ihc"],"trials":[],"people":["pasi-janne"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2016,"doi":"10.1200/JCO.2015.63.4600","pmid":"26729443","authors":"Awad MM, Oxnard GR, Jackman DM, et al.","paperType":"observational","findings":["MET exon 14 mutations in 28 of 933 non-squamous lung cancers, 3.0%.","Median age 72.5 years, 68% women, 36% never smokers.","Stage IV cases carry concurrent MET amplification and strong c-Met staining far more often than early-stage cases.","Deep response to crizotinib where the mutated allele was also amplified."],"whatItMeans":"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.","caveats":["Retrospective, from one institution's sequencing stream.","Twenty-eight positive cases.","Treatment evidence is a single response rather than a trial."],"changedPractice":false,"participants":6376},"route":"/key-papers/paper-awad-met-exon-14-mutations-lung-jco-2016/","neighbours":{"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"met","kind":"target","name":"MET","route":"/targets/met/"}],"drug":[{"id":"capmatinib","kind":"drug","name":"Capmatinib","route":"/drugs/capmatinib/"},{"id":"crizotinib","kind":"drug","name":"Crizotinib","route":"/drugs/crizotinib/"},{"id":"tepotinib","kind":"drug","name":"Tepotinib","route":"/drugs/tepotinib/"}],"institution":[{"id":"dana-farber","kind":"institution","name":"Dana-Farber Brigham Cancer Center","route":"/institutions/dana-farber/"}],"pathway":[{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}],"term":[{"id":"gene-amplification","kind":"term","name":"Gene amplification and copy-number change","route":"/terms/gene-amplification/"},{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"},{"id":"met-amplification","kind":"term","name":"MET amplification (bypass resistance)","route":"/terms/met-amplification/"},{"id":"met-exon-14-skipping","kind":"term","name":"MET exon 14 skipping mutation","route":"/terms/met-exon-14-skipping/"}],"person":[{"id":"pasi-janne","kind":"person","name":"Pasi A. Jänne","route":"/people/pasi-janne/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}],"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/"},{"id":"met-ex14","kind":"biomarker","name":"MET exon 14 skipping mutation","route":"/biomarkers/met-ex14/"}]}}