Abstract
Abstract
Purpose
Our previous study has shown that PTPRZ1-MET (ZM) fusion is a viable target for MET inhibitors in gliomas. However, the diversity and prevalence of somatic MET alterations in diffuse gliomas are still elusive and need to be extensively characterized for identifying novel therapeutic targets.
Methods
Totally, 1,350 glioma patients and 31 patient-derived cells were collected from the Chinese Glioma Genome Atlas (CGGA) and published data. All kinds of MET fusions and/or splicing variants (MET F/SVs) were identified by bioinformatical methods. Single-cell RNA sequencing (scRNA-seq) were used for validation. In vitro experiments of drug resistance were conducted for the possibility of MET-targeted treatment.
Results
MET F/SVs but not genomic amplification, were highly enriched in the secondary glioblastomas (sGBM) and marked worse prognosis. Further molecular and scRNA-seq analysis revealed that MET F/SVs were induced in the course of glioma evolution and highly associated with MET overexpression. Subsequent in vitro and the clinical study showed that cells and patients harboring MET F/SVs have better response to MET inhibitors.
Conclusion
Our findings expanded the percentage of gliomas with abnormal MET alterations and suggested that a subgroup of gliomas harboring MET F/SVs may benefit from MET-targeted therapy.
Funder
the Natural Science Foundation of China (NSFC)/Research Grants Council (RGC), Hong Kong, China Joint Research Scheme
the National Natural Science Foundation of China
the Mainland-Hong Kong Joint Funding Scheme ITC grant
MOST grant
Sino-German Center for Research Promotion
the Beijing Natural Science Foundation
the Beijing Nova Program
Publisher
Springer Science and Business Media LLC
Cited by
1 articles.
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