Fibroblast growth factor receptor 3 (FGFR3) aberrations in muscle-invasive urothelial carcinoma

Abstract

Background: Recent studies suggest that FGFR3 is a potential therapeutic target in urothelial carcinoma (UC). The purpose of this study was to evaluate the rates and types of FGFR3 aberrations in patients with muscle-invasive UC who received radical resection.

Methods: We analyzed surgical tumor samples from 74 UC patients who had received radical cystectomy (n = 40) or ureteronephrectomy (n = 34). Ion AmpliSeq Cancer Hotspot Panel v2 and nCounter Copy Number Variation Assay were used to detect FGFR3 aberrations.

Results: Fifty-four patients (73%) had high-grade tumors, and 62% had lymph node involvement. Sixteen patients (22%) harbored FGFR3 alterations, the most common of which was FGFR3 mutations (n = 13): Y373C (n = 3), N532D (n = 3), R248C (n = 2), S249C (n = 1), G370C (n = 1), S657S (n = 1), A797P (n = 1), and 746_747insG (n = 1). Three additional patients had a FGFR3-TACC3 rearrangement. The frequency of FGFR3 aberrations was higher in bladder UC (25%) than in UC of the renal pelvis and ureter (18%) but the difference was not statistically significant (P = 0.444). Genes that were co-aberrant with FGFR3 included APC (88%), PDGFRA (81%), RET (69%), and TP53 (69%).

Conclusions: We report the frequency and types of FGFR3 aberrations in Korean patients with UC. Patients with FGFR3 mutations or FGFR3-TACC3 fusion may constitute potential candidates for a novel FGFR-targeted therapy in the perioperative setting.

Keywords: FGFR; Fusion; Mutation; Urothelial carcinoma.

Fig. 1

Distribution of additional mutations identified by Ampliseq (n = 16). Red squares indicate inactivating mutation. Green squares indicate activating mutation. UTUC Upper tract urothelial carcinoma, UBUC Urinary bladder urothelial carcinoma