[Correlation of FGFR3 mutations and chromosomal alterations in bladder cancer].
It has been suggested that mutation of FGFR3 is associated with non-invasive tumors of low malignant potential and low risk of recurrence and progression. The aim of this study was to analyze the distribution of FGFR3 mutations in bladder tumors of different grade and stage and to determine the relation of FGFR3 mutations to chromosomal alterations detected by CGH. Frozen sections of 100 bladder cancer samples served as templates for manual microdissection. DNA was isolated from dissected samples containing at least 80% tumor cells. Mutations in FGFR3 were analyzed by SNaPshot analysis. CGH was carried out according to standard protocols. FGFR3 mutations were detected in 45 out of 92 samples (48.9 %). Concerning T-category, the following mutation frequencies occurred: pTa - 69 %, pT1 - 38 %, pT2/3 - 0 %. The mutation frequency was significantly associated with tumor grade: G1 - 72%, G2 - 56%, G3 - 4%. In pTaG1 tumors, mutations were found in 74 %. A significant lower number of genetic alterations per tumor detected by CGH was associated with FGFR3 mutations (2 vs. 8). This association was also seen in pTaG1 tumors: 2.5 (with mutation) vs. 7.5 (without mutation). Our results confirm that FGFR3 mutations characterize non-invasive low-risk tumors of low malignancy. The low malignant potential of these tumors is underlined by a low number of chromosomal alterations per tumor. Therefore, FGFR3 could represent a prognostic marker of chromosomally stable tumors with low malignant potential.
Junker
Kerstin
K
Klinik für Urologie, Universität, Jena.
van Oers
Johanna M M
JM
Zwarthoff
Ellen C
EC
Kania
Ines
I
Schubert
Joerg
J
Hartmann
Arndt
A
D002869:Chromosome Aberrations; D002877:Chromosomes, Human; D004252:DNA Mutational Analysis; D006801:Humans; D009154:Mutation; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology*
C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3