Abstract
In this age of targeted therapy, identification of molecular pathways that are deregulated in cancer will not only elucidate underlying tumorigenic mechanisms, but may also help to determine the classes of drugs that are used for treatment. In kidney cancer, a spectrum of histological subtypes exists that are characterized both by distinct molecular signatures and increasingly by distinct molecular pathways that are deregulated in each subtype. For example, the VHL/hypoxia pathway is well-known to be deregulated in clear cell renal cell carcinoma (RCC) whereas in papillary RCC activation of the HGF/Met pathway has been implicated. Additional molecular pathways, many not yet identified, may also be involved in the development of the different histologic subtypes. Moreover, differences in pathway activation may reflect differences in tumor progression and response to treatment. In this article, we describe an oncogenomic approach, based on integrative analysis of gene expression profiling data. In this approach, gene expression data is used to identify both cytogenetic abnormalities and molecular pathways that are deregulated in RCC. Ideally, predicted pathway abnormalities can be linked to predicted cytogenetic abnormalities to identify likely candidate genes. Although further cellular and functional studies are warranted to validate the computational models, development of such models in RCC have the potential to open up new avenues of molecular research and may have significant diagnostic and therapeutic implications.
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Acknowledgements
This work was supported by NIH Grant R33-CA10113-01 to KAF and the Van Andel Research Institute. We acknowledge The Gerber Foundation, Hauenstein Foundation, Fischer Family Trust, the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor, the Schregardus Family Foundation, and Amway Japan Limited. We thank the Cooperative Human Tissue Network of the National Cancer Institute for providing tumor samples for this research. We also thank Sabrina Noyes for administrative support.
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Furge, K., Tan, M., Dykema, K. et al. Identification of deregulated oncogenic pathways in renal cell carcinoma: an integrated oncogenomic approach based on gene expression profiling. Oncogene 26, 1346–1350 (2007). https://doi.org/10.1038/sj.onc.1210256
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DOI: https://doi.org/10.1038/sj.onc.1210256
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