Updated Molecular Analysis of MET Exon 14 Skipping Mutations (METex14) in Non-Small Cell Lung Cancer (NSCLC)
Jennifer Marks, Nishant Gandhi, Balazs Halmos, Suresh Ramalingam, Lyudmila Bazhenova, Melina Marmarelis, Joanne Xiu, Phillip Walker,
Matthew Oberley, Patrick Ma, Stephen Liu
MET is a proto-oncogene that plays a central role in cell proliferation and survival•Somatic mutations impacting exon 14 alternative splicing can lead to skipping the transcription of the Y1003 loci which is critical for the regulation of MET activation
MET exon 14 skipping mutations (METex14) are now established therapeutic targets in non-small cell lung cancer (NSCLC)
There is notable heterogeneity in METex14, which occurs in smokers and non-smokers and both squamous (Sq) and non-squamous (nSq) histology
We aimed to explore the heterogeneous mutational landscape within METex14 NSCLC by specific mutation, histology, and smoking status
There is significant heterogeneity within METex14 NSCLC, with differences in co-mutations, TMB, and PD-L1 expression noted among different METex14 mutations. While METex14 is detected in both squamous and non-squamous NSCLC, there are differences in the enrichment of oncogenic pathways, which may explain the heterogeneity in response to various treatments. Future studies investigating specific METex14 alterations may allow more granular personalization of treatment for patients with METex14 NSCLC.