Real-world genomic landscape of FGFR2 amplifications and fusions in solid tumors: analysis of 4,953 patients using clinical-grade NGS

Abstract

Fibroblast growth factor receptor 2 (FGFR2) alterations, including amplifications and fusions, are actionable oncogenic drivers in multiple cancers, but their prevalence and genomic features are not well defined. Between October 2019 and October 2024 at Samsung Medical Center, 4,953 patients with solid tumors underwent next-generation sequencing using TruSight Oncology 500 (TSO 500) assays as part of routine clinical practice. We surveyed the incidence of FGFR2 alterations including amplifications (copy number variations) and fusions, as well as their genomic profiles. Among the 4,953 solid cancer patients, 66 patients (1.3%) had FGFR2 amplifications and 39 (0.8%) had FGFR2 fusions. The most common tumor type associated with FGFR2 amplification was gastric cancer (78.8%), while cholangiocarcinoma (51.3%) and gastric cancer (28.2%) were the predominant subtypes among fusion-positive patients. TP53 mutations were frequently observed in FGFR2-amplified tumors (69.7%). Among the 39 patients with FGFR2 fusions, BICC1 was the most frequent partner gene. 488 patients (9.9%) showed FGF family amplifications. A significant positive correlation was observed between FGFR2 and FGF amplification copy number levels ( r = 0.64, p = 0.0057). We demonstrated that 1.8% of solid tumors harbored FGFR2 alterations: amplifications (1.3%) were enriched in gastric cancer, while fusions (0.8%) were most frequent in cholangiocarcinoma. Amplified tumors commonly co-mutated TP53, and most FGFR2-altered cases were microsatellite-stable with low tumor mutational burden. These findings highlight the value of FGFR2 profiling in routine clinical sequencing and may inform the design of future prospective studies of FGFR2-directed and combination approaches.