Analysis of MET kinase domain rearrangement in NSCLC

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 145; pp. 140 - 143
• Main Authors: Zhuo, Minglei, Liang, Zhen, Yi, Yuting, Wu, Nan, Yang, Xue, Zhong, Jia, Chen, Xiaohan, Huang, Yi, Yu, Zicheng, Liu, Chang, Zeng, Xiaoling, Gu, Wenguang, Zhao, Jun
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.07.2020
• Subjects: Kinase domain rearrangement (KDRE); MET; Non-small-cell lung cancer; Targeted sequencing; PR; NSCLC; MET KDRE; Non-small-cell lung cancer; VAF; MET KDD; Kinase domain rearrangement (KDRE); NGS; Targeted sequencing; CGP; MET
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2020.04.040

•MET KDRE distribution in NSCLC characterized in a large-scale Chinese population•Plasma, tissue and pleural effusion were all feasible for MET fusion analysis by NGS•Novel targets identified for developing therapies for patients with MET KDRE 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. 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. 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. 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.