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Published on: May 7, 2020
MET Exon 14 Skipping in Non-Small Cell Lung Cancer
Rebecca S Heist1, Hyo Sup Shim2, Shalini Gingipally3
1Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA rheist@partners.org.
Background:
Non-small cell lung cancers (NSCLCs) harboring specific genetic alterations can be highly sensitive to targeted therapies.
Materials And Methods:
We performed a targeted rearrangement assay on 54 NSCLCs across all stages that were from patients who were never smokers and did not have driver mutations. Because MET exon 14 skipping was the most frequent alteration found, we surveyed the results for MET exon 14 skipping at Massachusetts General Hospital (MGH) since the inclusion of this alteration into our current molecular profiling panel.
Results:
In a cohort of 54 never-smokers with lung cancers that were wild-type for known driver mutations, MET exon 14 skipping was the most frequently recurring alteration, occurring in 10 cancers (19%). Clinical testing at MGH via our next-generation sequencing (NGS) and NGS-rearrangement panels showed an additional 16 cases of MET exon 14 skipping, for an overall estimated frequency of 5.6%. A clinical case of a patient with MET exon 14 skipping treated with the MET inhibitor crizotinib is also described.
Conclusion:
MET exon 14 skipping is a targetable gene alteration found in NSCLC. Patients with these alterations may respond well to MET inhibition.
Implications For Practice:
MET exon 14 skipping occurs with an approximately 5% frequency in NSCLC and is seen in both squamous and adenocarcinoma histology. Patients whose cancers have MET exon 14 skipping can respond well to MET inhibitors. Molecular testing for MET exon 14 skipping should be performed on all lung cancers because this is a targetable alteration.
Insights
MET exon 14 skipping is a targetable genetic alteration in non-small cell lung cancer (NSCLC). This finding suggests that MET inhibitors may effectively treat patients with this specific NSCLC subtype.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) exhibits sensitivity to targeted therapies based on specific genetic alterations.
- Identifying actionable mutations is crucial for effective NSCLC treatment strategies.
Purpose of the Study:
- To investigate the frequency and clinical significance of MET exon 14 skipping alterations in NSCLC.
- To evaluate the potential of MET inhibitors for patients with MET exon 14 skipping.
Main Methods:
- A targeted rearrangement assay was conducted on 54 NSCLC samples from never-smokers without driver mutations.
- Retrospective analysis of MET exon 14 skipping cases identified through molecular profiling at Massachusetts General Hospital (MGH).
Main Results:
- MET exon 14 skipping was the most frequent alteration in the studied cohort, found in 19% of never-smokers.
- Overall frequency of MET exon 14 skipping in NSCLC was estimated at 5.6% through clinical testing.
- A case report details a patient with MET exon 14 skipping successfully treated with the MET inhibitor crizotinib.
Conclusions:
- MET exon 14 skipping represents a targetable driver alteration in NSCLC.
- Patients with MET exon 14 skipping may benefit from MET-targeted therapies.
- Molecular testing for MET exon 14 skipping is recommended for all NSCLC patients to identify potential treatment candidates.
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