A large-scale, multi-center molecular characterization of MET fusions in a real-world Chinese population

3064 Background: MET is a driver gene notable in its diversity of clinically relevant aberrations, including exon 14 skipping, copy number gain, point mutations, and gene fusions. Compared with the former two, MET fusions are severely under-reported, leaving unanswered a series of fundamental questions. In this study, we addressed this knowledge gap by screening for and characterizing MET fusions in a real-world, multi-center population of Chinese cancer patients. Methods: We retrospectively included patients with solid tumors and available genome profiles acquired between August 2015 to May 2021. MET fusion-positive ( MET+) patients were subsequently selected for clinical and molecular characterization. Results: A total of 79816 patients across 27 tumor types were screened. We detected 155 putative MET fusions from 122 patients, resulting in an overall prevalence of 0.15%. Lung cancer comprised the majority of MET+ patients (92, 75.4%). Prevalence was markedly higher in liver, biliary tract cancer, and renal cancer (range 0.52%-0.60%) and lower in ovarian cancer (0.06%). A substantial proportion (48/58, 82.8%) of unique partners were reported for the first time. The fusion partners also turned out to be highly heterogeneous, with ST7, HLA-DRB1, and KIF5B as the three most common partners. Mutational landscape analysis of lung adenocarcinoma patients (n = 32) revealed high prevalence of aberrant TP53 in MET+ patients as well as EGFR L858R, L861Q and MET amplification as concurrent alterations. Conclusions: This study is, to our knowledge, currently the largest in characterizing MET fusions. Our findings warrant further clinical validation and mechanistic study that may translate into therapeutic avenues for MET fusion-positive cancer patients.