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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.
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.
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.
Shares MET amplification (gene copy number), Pasi A. Jänne, MET amplification (bypass resistance), Gene amplification and copy-number change.
Shares MET exon 14 skipping mutation, MET exon 14 skipping mutation, MET, Receptor tyrosine kinase activation.
Shares c-Met protein overexpression (IHC 3+ in >= 50% of tumour cells), MET exon 14 skipping mutation, MET amplification (gene copy number), MET amplification (bypass resistance).
Shares Tepotinib, Capmatinib, Crizotinib, MET.
Shares MET amplification (gene copy number), MET amplification (bypass resistance), MET, Receptor tyrosine kinase activation.
Shares Pasi A. Jänne, MET, Dana-Farber Brigham Cancer Center, Receptor tyrosine kinase activation.
Shares MET exon 14 skipping mutation, MET, Immunohistochemistry (IHC), Receptor tyrosine kinase activation.
Shares Capmatinib, MET amplification (bypass resistance), Crizotinib, MET.