771: Low Frequency of Chromosomal Alterations in CGH Analysis in Low-Risk Papillary Bladder Tumors with FGFR3 Mutations

Abstract

Proc Amer Assoc Cancer Res, Volume 47, 2006 4205 FGFR3 was shown to be mutated frequently in bladder cancer. Furthermore, it was suggested, that mutation of FGFR3 is associated with non-invasive tumors of low malignant potential and low risk of recurrence and progression. We hypothesize that FGFR3-mutated tumors are more genetically stable than bladder tumors without mutation.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 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. Results of mutation analysis were obtained from 92 samples. FGFR3 mutations were detected in 45 samples (48.9%). Concerning T-category, the following mutation frequencies occurred: pTa- 61%, pT1-40%, pT2/3- 0%. The mutation frequency was also significantly associated with tumor grade: G1-70%, G2-46%, G3-4%. In pTaG1 tumors, mutations were found in 72%. A significantly lower number of genetic alterations per tumor detected by CGH was associated with FGFR3 mutations (3.3 vs. 10 alterations per tumor ). This association was also seen in pTaG1 tumors: 3.2 (with mutation) vs. 6.8 (without mutation). In pTa/pT1 tumors gain of 8q was detected more frequently in non-mutated tumors (86% vs. 25%). 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 genetic alterations per tumor. Therefore, FGFR3 represents a valuable prognostic marker of tumors with low malignant potential and could be used as surrogate marker for detection of genetic stable bladder tumors with good clinical outcome.