MET exon 14 skipping

MET exon 14 skipping is a mutation in the MET gene that causes a section of the gene (exon 14) to be left out when the cell builds the MET protein. The resulting protein cannot be turned off normally, so it keeps signaling cancer cells to grow. It is found in roughly 3–4% of non–small cell lung cancers, most often in older patients and in a lung cancer subtype called pulmonary sarcomatoid carcinoma.

Origin

The MET gene was identified in 1984 by Cooper and colleagues from a chemically transformed human cell line and named for its discovery in a methyl-nitro-nitrosoguanidine experiment. MET exon 14 skipping was recognized as a distinct cancer-driving alteration in the 2000s, and the FDA approved the first targeted therapies for it (capmatinib and tepotinib) in 2020.

Significance in Asbestos Context

For patients with lung cancer and a history of asbestos exposure, MET exon 14 skipping is one of the actionable mutations that should be looked for on comprehensive biomarker (molecular) testing of a tumor biopsy. If present, it opens the door to oral targeted therapies (MET inhibitors) that often work better and are easier to tolerate than chemotherapy. Asbestos-related lung cancer is treated like other non–small cell lung cancers, so the same molecular testing standards apply, and identifying this alteration can meaningfully change treatment, prognosis, and quality of life. It does not affect whether asbestos caused the cancer; causation depends on exposure history and the Helsinki Criteria, not on which driver mutation the tumor carries.

Example Sentence

After her lung cancer biopsy came back positive for MET exon 14 skipping, her oncologist switched her from standard chemotherapy to a targeted MET inhibitor taken as a daily pill.

Related Terms

Non-Small Cell Lung Cancer, Targeted Therapy, Biomarker Testing, Pulmonary Sarcomatoid Carcinoma, Driver Mutation, EGFR Mutation

Notes

• If you have been diagnosed with non–small cell lung cancer, ask your oncologist whether your tumor has been tested with a comprehensive next-generation sequencing (NGS) panel that includes MET exon 14. Single-gene tests can miss it.
• Request that enough tissue from your biopsy be preserved for full molecular testing before any is used up; if tissue is limited, ask about a blood-based (liquid biopsy) test.
• FDA-approved targeted therapies for this alteration include capmatinib (Tabrecta) and tepotinib (Tepmetko); ask whether either is appropriate and whether clinical trials are available.
• Keep copies of your pathology and molecular testing reports. They document your diagnosis and treatment choices, which may be relevant to both medical care and any asbestos-related legal claim.