MET exon 14 mutations represent a clinically unique molecular subtype of non-small-cell lung cancer (NSCLC), according to a study of next-generation sequencing result from 6,376 cancers. Researchers found:

• MET exon 14 mutations were seen in 3.0% of nonsquamous NSCLCs and were not seen in other cancer types in this study.

• Patients with MET exon 14-mutated NSCLC were significantly older (72.5 years) than patients with EGFR-mutant (61 years) or KRAS-mutant NSCLC (65 years).

• Among patients with MET exon 14 mutations, 68% were women, and 36% were never-smokers.

• Stage IV MET exon 14-mutated NSCLCs were significantly more likely to have concurrent MET genomic amplification and strong c-Met immunohistochemical expression than stage IA to IIIB MET exon14-mutated NSCLCs and stage IV MET exon 14-wild-type NSCLCs.

• A patient whose lung cancer harbored a MET exon 14 mutation with concurrent genomic amplification of the mutated MET allele had a major partial response to the c-Met inhibitor crizotinib.

Citation: Awad MM, Oxnard GR, Jackman DM, et al. 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. [Published online ahead of print January 4, 2016]. J Clin Oncol. doi:10.1200/JCO.2015.63.4600.