Molecular and clinicopathological characteristics of EGFR gene fusions in 35,023 Chinese patients with solid tumors

Abstract Epidermal growth factor receptor (EGFR) fusions are rare but potentially actionable oncogenic drivers across multiple solid tumors. Here, we assessed the incidence of EGFR fusions and described their impact on prognosis in solid tumors. Panel-based next-generation sequencing (NGS) data of 35,023 patients with different types of solid tumors were collected and analyzed from the Simcere Diagnostics (Nanjing, China) database. A 9563-patient cohort was derived from The Cancer Genome Atlas (TCGA) to explore the relationship between EGFR fusion status and overall survival (OS). In our cohort, 0.303% (106/35016) of patients harbored EGFR fusions. The frequencies of EGFR fusions were different in diverse tumor types, ranging from 0.034–1.613%. Gastroesophageal junction cancer had the highest frequency of fusion (1.613%), followed by medatloblastoma (1.515%) and glioma (1.370%). The fusion partner gene is also different in various cancer types. The top 3 genes that comutated with EGFR fusion were TP53 (mutation frequency, MF: 65%), BRCA2 (MF: 43%), and ALK (MF: 41%). In the TCGA cohort, patients in the EGFR fusion group had a significantly shorter OS than those in the non-EGFR fusion group (p < 0.0001), suggesting that EGFR fusion might be a high-risk factor for poor prognosis. Our study is the first retrospective analysis of EGFR fusions in a large-scale solid tumor population, which may provide a reference for future EGFR-TKI clinical trials with EGFR fusions.