Fibroblast growth factor receptor 3 mutations in bladder tumors correlate with low frequency of chromosome alterations.

The aim of this study was to analyze the distribution of FGFR3 mutations in bladder tumors of different grade and stage and determine the relation of mutations to chromosomal alterations detected by comparative genomic hybridization (CGH). One hundred 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 of 92 samples (48.9%). Concerning T-category, the following mutation frequencies occurred: pTa, 69%; pT1, 38%; and pT2-3, 0%. The mutation frequency was significantly associated with tumor grade: G1, 72%; G2, 56%; and G3, 4%. In pTaG1 tumors, mutations were found in 74%. A significantly 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). FGFR3 mutations characterize noninvasive low-risk tumors of low malignancy. The low malignant potential of these tumors is underlined by a low number of genetic alterations per tumor. Therefore, FGFR3 represents a valuable prognostic marker of tumors with low malignant potential and can be used as surrogate marker for the detection of genetically stable bladder tumors.

[Correlation of FGFR3 mutations and chromosomal alterations in bladder cancer]. / Korrelation von FGFR3-Mutationen und chromosomalen Veränderungen in Harnblasentumoren.

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.