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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
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Uncommon MET mutational landscape in a non-small cell lung cancer patient treated with crizotinib: Case report
Margaux Geier1, Jessica Nguyen1, Estelle Dhamelincourt1
1Department of Medical Oncology, CHRU Morvan, University Hospital of Brest, Brest, France.
Background:
MET exon 14 (METex14) skipping mutations are oncogenic drivers observed in approximately 3-4% of non-small cell lung cancers (NSCLC). Several distinct genetic alterations leading to METex14 have been reported but clinical significances of rare mutations are not well defined as well as outcomes of patients upon MET inhibitors (METi).
Case Presentation:
This report presents the case of a patient with metastatic NSCLC harboring an uncommon MET mutational landscape including notably a novel METex14 mutation (R1022L). Dramatic but transient efficacy was observed under crizotinib, due to early occurrence of acquired both on- and off-target mechanisms of resistance such as MET D1246H mutation and wild-type KRAS amplification.
Conclusion:
Our case provides additional data on MET rare oncogenic variants and their sensitivity to METi. Systematic assessment of post-tyrosine kinase inhibitor tumor sample remains critical to identify on- and off-target mechanisms that may represent therapeutically targetable drivers in resistant patients.
Insights
Rare MET exon 14 skipping mutations in non-small cell lung cancer (NSCLC) present unique challenges. This case highlights transient efficacy of MET inhibitors and acquired resistance mechanisms, emphasizing the need for further research.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MET exon 14 skipping mutations drive 3-4% of non-small cell lung cancers (NSCLC).
- Clinical significance of rare MET mutations and patient outcomes with MET inhibitors (METi) are not well-defined.
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