Abstract 3497: Fibroblast growth factor receptor 3 (FGFR3) aberrations in muscle-invasive urothelial carcinoma

Abstract

Abstract Purpose: Muscle-invasive urothelial carcinoma (UC) has a poor prognosis and novel approaches to systemic therapy are required. Recent studies show that FGFR3 activation is an important contributor to tumor development and angiogenesis in UC. Therefore, FGFR3 is a potential therapeutic target in UC. The purpose of this study was to evaluate the rates and types of FGFR3 aberrations in invasive UC. Methods: We analyzed primary 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). These mutations included Y373C (n=3), N532D (n=3), R248C (n=2), S249C (n=2), G370C (n=1), A797P (n=1), and 746_747insG (n=1). In all three patients with FGFR3 rearrangement, the fusion partner was TACC3. The frequency of FGFR3 aberrations was higher in bladder UC (28%) than in UC of the renal pelvis and ureter (15%), but the difference was not statistically significant (P=0.183). Genes that were co-aberrant with FGFR3 included APC (88%), PDGFRA (81%), RET (69%), and TP53 (69%). Conclusions: FGFR3 abnormalities are less frequently seen in upper tract UC than bladder UC. Patient selection could be critical in designing new approaches for anti-FGFR3 therapy in the perioperative setting. Citation Format: Young Saing Kim, Soon Il Lee, Se Hoon Park. Fibroblast growth factor receptor 3 (FGFR3) aberrations in muscle-invasive urothelial carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3497.