Analysis of MET kinase domain rearrangement in NSCLC

Abstract Objectives Many MET rearrangements have been identified in various tumor types. However, the frequencies and characteristics of MET rearrangements are not well defined in non-small-cell lung cancer (NSCLC). We sought to illustrate the distribution of MET kinase domain rearrangements (KDREs) in NSCLC, and to uncover novel targets for further drug development in these patients. Materials and methods Targeted sequencing using a 1021-gene panel or a 59-gene panel was performed in 5965 NSCLC cases. We sequenced all MET exons and used bioinformatics techniques to identify fusions. Results Fifteen MET KDREs were identified from all patients. The incidence of MET KDRE was 0.26% (15/5695) in the cohort; 60% (9/15) of the fused partners were the genes upstream or downstream of MET. All the fusions of the MET gene with upstream genes or specific regions within them were due to inversions, while the fusions with downstream genes or their encompassed regions were caused by duplications or intra-chromosomal translocations. In the MET KDRE-positive NSCLC cases who did not receive targeted therapies, 75% (6/8) harbored no actionable mutation referring to the NCCN guideline. Conclusion Our study illustrated the MET KDRE in NSCLC cases among the Chinese population and unearthed novel targets to develop new effective therapies for patients with MET KDRE.