Minglei Zhuo1, Zhen Liang2, Yuting Yi3, Nan Wu4, Xue Yang1, Jia Zhong1, Xiaohan Chen1, Yi Huang5, Zicheng Yu5, Chang Liu3, Xiaoling Zeng3, Wenguang Gu3, Jun Zhao6. 1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department I of Thoracic Oncology, Peking University Cancer Hospital & Institute, No.52, Fucheng Road, Haidian District, Beijing, China. 2. Department of Thoracic Surgery I, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China. 3. Geneplus-Beijing, Beijing 102206, China. 4. Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China. 5. Geneplus-Shenzhen Genomics Institute, Shenzhen 518000, China. 6. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department I of Thoracic Oncology, Peking University Cancer Hospital & Institute, No.52, Fucheng Road, Haidian District, Beijing, China. Electronic address: junzhaobjmu@sina.com.
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.
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.
Authors: Huanhuan Sun; Hong Zhang; Yan Yan; Yushi Li; Gang Che; Cuiling Zhou; Christophe Nicot; Haiqing Ma Journal: Mol Cancer Date: 2022-02-18 Impact factor: 27.401