{"entity":{"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","aka":[],"tldr":"This large sequencing study defined MET exon 14 skipping as a recurrent driver in about 3 percent of lung adenocarcinomas and other cancers, showed the mutations are diverse and easily missed, and reported patients responding to MET inhibitors.","summary":"Analysis of comprehensive genomic profiling from more than 38,000 tumours identifying MET exon 14 splice-site alterations in about 3 percent of lung adenocarcinomas and at lower frequency in other tumours, characterising the wide range of DNA changes involved, and describing responses to crizotinib and capmatinib in patients harbouring them.","asOf":"2026-09-17","links":[{"label":"Cancer Discov 2015","url":"https://doi.org/10.1158/2159-8290.CD-15-0285"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25971938/"}],"tags":[],"related":["met-ex14"],"cancers":["met-altered-nsclc","nsclc"],"sections":[],"technologies":["cgp"],"targets":["met"],"drugs":[],"companies":[],"institutions":[],"pathways":["rtk-activation"],"terms":["met-exon-14-skipping"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2015,"doi":"10.1158/2159-8290.CD-15-0285","pmid":"25971938","authors":"Frampton GM, Ali SM, Rosenzweig M, et al.","paperType":"translational","findings":["MET exon 14 alterations in about 3 percent of lung adenocarcinomas, more common in older patients and in sarcomatoid histology.","Clinical responses to MET inhibitors in patients with the alteration."],"whatItMeans":"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.","caveats":["Retrospective sequencing database with case reports of response."],"changedPractice":true},"route":"/key-papers/paper-frampton-met-exon-14-cancer-discov-2015/","neighbours":{"biomarker":[{"id":"met-ex14","kind":"biomarker","name":"MET exon 14 skipping mutation","route":"/biomarkers/met-ex14/"}],"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/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"}],"target":[{"id":"met","kind":"target","name":"MET","route":"/targets/met/"}],"pathway":[{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}],"term":[{"id":"met-exon-14-skipping","kind":"term","name":"MET exon 14 skipping mutation","route":"/terms/met-exon-14-skipping/"}],"journal":[{"id":"cancer-discovery","kind":"journal","name":"Cancer Discovery","route":"/journals/cancer-discovery/"}],"paper":[{"id":"paper-wolf-geometry-mono-1-capmatinib-nejm-2020","kind":"paper","name":"Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer","route":"/key-papers/paper-wolf-geometry-mono-1-capmatinib-nejm-2020/"}]}}