MET exon 14 splicing alterations across tumour types and their sensitivity to MET inhibitors
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.
Overview
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.
- 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.
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.
- Retrospective sequencing database with case reports of response.