Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Bladder carcinoma [C67.9]

OMIM numbersr: 109800,FGFR3 (134934)

Dipl.-Ing. (FH) Tanja Hinrichsen,
Prof. Dr. med. Barbara Dockhorn-Dworniczak

Scientific Background

Bladder cancer is the seventh most common type of cancer worldwide. In Germany, approximately 15,500 people develop bladder cancer annually, of which a third are women. The predominant form of bladder cancer is urothelial carcinoma, which often occurs simultaneously at various points in the bladder and the urinary tract. The rate of disease increases with increasing age; the average age at diagnosis is 73 years.

Although cystoscopy is still the best method to diagnose bladder carcinoma, detecting 90% of the lesions, it is an invasive and uncomfortable method which is followed by transurethral resection of the bladder tumor (TURBT). After initial TURBT, 50-70% of patients with non-muscle-invasive bladder cancer (NMIBC) will experience multiple relapses, whilst in 10-20% of these patients the disease will progress into muscle-invasive bladder cancer (MIBC).

NMIBC and MIBC are genetically distinct. Whilst NMIBC is characterized by a high number of mutations in FGFR3 which lead to the constitutive activation of the RAS/MAPK signal pathway, MIBC exhibits primarily mutations in TP53. In general mutations in FGFR3 and TP53 are mutually exclusive, thus it can be presumed they develop differently. However, these mutations often occur simultaneously in Stage pT1 tumors.

Mutations in FGFR3 occur in approximately 50% of tumors of the upper and lower urinary tract. They seem to occur early in urothelial transformation, so that they can be detected in approximately 80% of pre-neoplastic lesions. Therefore, FGFR3 mutations can be used as urine biomarkers for recurrent disease, especially in low grade disease.

In the future, pan-FGFR inhibitors could also have a role in targeted therapy.