No mutations of FGFR3 in normal urothelium in the vicinity of urothelial carcinoma of the bladder harbouring activating FGFR3 mutations in patients with bladder cancer

Otto, Wolfgang and Denzinger, Stefan and Bertz, Simone and Gaumann, Andreas and Wild, Peter J. and Hartmann, Arndt and Stoehr, Robert (2009) No mutations of FGFR3 in normal urothelium in the vicinity of urothelial carcinoma of the bladder harbouring activating FGFR3 mutations in patients with bladder cancer. INTERNATIONAL JOURNAL OF CANCER, 125 (9). pp. 2205-2208. ISSN 0020-7136, 1097-0215

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Abstract

Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene causing constitutive oncogenic protein activation have been shown to be frequent in papillary noninvasive bladder tumours and are associated with a low risk of progression and a favourable outcome. FGFR3 alterations have also been found in benign urothelial papilloma and flat urothelial hyperplasia suggesting FGFR3 alterations as an early event in bladder tumorigenesis. To date there is no data available on FGFR3 mutations in normal urothelium from patients with bladder cancer. We therefore analysed 64 samples of histopathological unsuspicious normal urothelium from 38 patients with FGFR3 mutated bladder tumours and 15 samples of urothelium from patients (n = 15) without any urothelial malignancy as a control group. Urothelial cells were microdissected from formalin-fixed, paraffin-embedded material. After DNA isolation whole genome amplification was done by I-PEP-PCR. FGFR3 mutations were detected using SNaPshot analysis. All samples could successfully be investigated. FGFR3 analyses did not reveal any mutation in the urothelium from neither the control group nor the bladder cancer group. All urothelial samples showed a wildtype sequence for FGFR3. These data suggest that mutations in the FGFR3 gene are not the earliest genetic alterations in bladder carcinogenesis and are associated with a hyperproliferative (hyperplastic) phenotype in the urothelium. Chromosomal alterations like deletions on chromosome 9q or aberrant promoter hypermethylation could play more important roles in early urothelial transformation than mutational FGFR3 activation. (C) 2009 UICC

Item Type: Article
Uncontrolled Keywords: GROWTH-FACTOR RECEPTOR-3; GRADE; CHROMOSOME-9; DELETIONS; SURVIVAL; FREQUENT; TUMORS; bladder cancer; FGFR3; normal urothelium
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Pathologie
Medicine > Lehrstuhl für Urologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 02 Sep 2020 09:08
Last Modified: 02 Sep 2020 09:08
URI: https://pred.uni-regensburg.de/id/eprint/28197

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