Molecular characterization ofMETfusions from a large real‐world Chinese population: A multicenter study

Abstract

AbstractPurposeMETis 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.MethodsWe 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.ResultsWe 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.ConclusionTo 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.