Journal
ONCOGENE
Volume 25, Issue 18, Pages 2685-2696Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1209249
Keywords
expression profiling; FGFR3; chromosome 9; urothelial carcinoma; bladder cancer
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We used gene expression pro. ling, mutation analyses of FGFR3 and TP53, and LOH analyses of chromosome 9 and the TP53 region on chromosome arm 17p, to molecularly characterize 75 Ta and T1 bladder carcinomas. We identified four major cellular processes related to cell cycle, protein synthesis, immune response, and extra cellular components that contribute to the expressional heterogeneity of early-stage urothelial cell carcinoma ( UCC). Activating FGFR3 mutations were found at the highest frequency in G1 tumors ( 80%), and showed a strong correlation with FGFR3 expression. In contrast, G3 tumors displayed mutations in less than 10% of the cases and a low level of FGFR3 expression. Even though LOH on chromosome 9 was not associated with any specific expression pattern, our data indicate that loss of chromosome 9 is associated with tumor development rather than initiation. The combined analyses suggest the existence of two types of UCC tumors, one which is characterized by FGFR3 mutation or expression, high expression of protein synthesis genes, and low expression of cell cycle genes. Furthermore, the presented data underscore FGFR3 receptor involvement in urothelial cell transformation as the presence of FGFR3 mutations has a major impact on the global gene expression pro. le of bladder carcinomas.
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