# MET exon 14 splicing alterations across tumour types and their sensitivity to MET inhibitors

Source: https://onco.cc/key-papers/paper-frampton-met-exon-14-cancer-discov-2015/  
OnCo record `paper-frampton-met-exon-14-cancer-discov-2015` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: Cancer Discovery
- Year: 2015
- DOI: 10.1158/2159-8290.CD-15-0285
- Authors: Frampton GM, Ali SM, Rosenzweig M, et al.
- 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.
- What it means: 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.

## Sources

- Cancer Discov 2015: https://doi.org/10.1158/2159-8290.CD-15-0285
- PubMed: https://pubmed.ncbi.nlm.nih.gov/25971938/

## Connected records

- cancers: [MET exon 14 and MET-amplified non-small-cell lung cancer](https://onco.cc/cancers/met-altered-nsclc/)
- journals: [Cancer Discovery](https://onco.cc/journals/cancer-discovery/)

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