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Updated: Dec 20, 2025
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Analysis of MET kinase domain rearrangement in NSCLC
Minglei Zhuo1, Zhen Liang2, Yuting Yi3
1Key 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.
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.
Insights
MET kinase domain rearrangements (KDREs) occur in 0.26% of non-small-cell lung cancer (NSCLC) cases. These rearrangements, often involving adjacent genes, present potential new therapeutic targets for NSCLC patients.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- MET rearrangements are observed in various cancers, but their prevalence and nature in non-small-cell lung cancer (NSCLC) remain unclear.
- Understanding MET alterations is crucial for identifying new therapeutic strategies in NSCLC.
Purpose of the Study:
- To determine the frequency and characteristics of MET kinase domain rearrangements (KDREs) in a large cohort of NSCLC patients.
- To identify novel therapeutic targets for NSCLC patients with MET KDREs.
Main Methods:
- Targeted sequencing of a 1021-gene or 59-gene panel was performed on 5965 NSCLC cases.
- Bioinformatics analysis was employed to identify MET gene fusions and rearrangements across all MET exons.
Main Results:
- Fifteen MET KDREs were detected, with an overall incidence of 0.26% in the NSCLC cohort.
- Sixty percent of identified fusions involved genes located upstream or downstream of MET, resulting from inversions, duplications, or translocations.
- A significant proportion (75%) of MET KDRE-positive NSCLC patients without targeted therapy lacked other actionable mutations per NCCN guidelines.
Conclusions:
- This study provides a comprehensive overview of MET KDREs in the Chinese NSCLC population.
- The findings highlight MET KDREs as a potential target for novel drug development in NSCLC.
- Identifying these rearrangements can guide treatment decisions for a subset of NSCLC patients.
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