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

BMC Urol. 2018 Jul 31;18(1):68. doi: 10.1186/s12894-018-0380-1.

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Transitional Cell / genetics*
  • Carcinoma, Transitional Cell / metabolism
  • Carcinoma, Transitional Cell / pathology
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Invasiveness
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics*
  • Receptor, Fibroblast Growth Factor, Type 3 / metabolism
  • Urinary Bladder Neoplasms / diagnosis
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism

Substances

  • DNA, Neoplasm
  • Receptor, Fibroblast Growth Factor, Type 3