Molecular characterization ofMET fusions from a large real‐world Chinese population: A multicenter study
Hui Xia, Junhua Zhang, Tong Chen, Mingzhao Wang, Dongna Chen, Tongguo Si, Yutao Liu - Cancer Research
- Radiology, Nuclear Medicine and imaging
- Oncology
Abstract
Purpose
METis a notable driver gene in the diversity of aberrations with clinical relevance, including exon 14 skipping, copy number gain, point mutations, and gene fusions. Compared with the former two,METfusions are severely under‐reported, leaving a series of unanswered questions. In this study, we addressed this gap by characterizingMETfusions in a large, real‐world Chinese cancer population.
Methods
We retrospectively included patients with solid tumors who had DNA‐based genome profiles acquired through targeted sequencing from August 2015 to May 2021.METfusion‐positive (MET+) patients were subsequently selected for clinical and molecular characterization.
Results
We screened 79,803 patients across 27 tumor types and detected 155 putativeMETfusions from 122 patients, resulting in an overall prevalence of 0.15%. Lung cancer comprised the majority ofMET+ patients (92, 75.4%). Prevalence was markedly higher in liver cancer, biliary tract cancer, and renal cancer (range 0.52%–0.60%). It was lower in ovarian cancer (0.06%). A substantial proportion (48/58, 82.8%) of unique partners were reported for the first time. High heterogeneity was observed for partners, withST7,HLA‐DRB1, andKIF5Bas the three most common partners. Mutational landscape analysis of lung adenocarcinoma (n = 32) revealed a high prevalence ofTP53inMET+ alterations,EGFRL858R,EGFRL861Q, andMETamplification.
Conclusion
To our knowledge, this is currently the largest study in characterizingMETfusions. Our findings warrant that further clinical validation and mechanistic study may translate into therapeutic avenues forMET+ cancer patients.