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  • Oncogenomics
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Molecular characterization of early-stage bladder carcinomas by expression profiles, FGFR3 mutation status, and loss of 9q

Oncogene volume 25, pages 2685–2696 (2006)Cite this article

Abstract

We used gene expression profiling, 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 profile of bladder carcinomas.

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Acknowledgements

This study was supported by the Swedish Cancer Society, The Gunnar, Arvid and Elisabeth Nilsson Foundation, The Crafoord Foundation, the John and Augusta Persson Foundation, the IngaBritt and Arne Lundberg Foundation, the Maud and Birger Gustavsson Foundation, and the Petrus and Augusta Hedlund Foundation. The microarray facility was supported by the Knut and Alice Wallenberg Foundation via the Swegene Program.

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Authors and Affiliations

  1. Department of Clinical Genetics, Lund University Hospital, Lund, Sweden

    D Lindgren, A Andersson, T Fioretos & M Höglund

  2. Department of Urology, Lund University Hospital, Lund, Sweden

    F Liedberg, S Gudjonsson & W Månsson

  3. Department of Pathology and Cytology, Helsingborg Hospital AB, Helsingborg, Sweden

    G Chebil

  4. Department of Oncology, Lund University Hospital, Lund, Sweden

    Å Borg

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  1. D Lindgren
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  2. F Liedberg
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Correspondence to D Lindgren.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Lindgren, D., Liedberg, F., Andersson, A. et al. Molecular characterization of early-stage bladder carcinomas by expression profiles, FGFR3 mutation status, and loss of 9q. Oncogene 25, 2685–2696 (2006). https://doi.org/10.1038/sj.onc.1209249

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