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Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 February 2001, Vol. 97, No. 3, pp. 729-736 NEOPLASIA Activated fibroblast growth factor receptor 3 is an oncogene that contributes to tumor progression in multiple myeloma Marta Chesi, Leslie A. Brents, Sarah A. Ely, Carlos Bais, Davide F. Robbiani, Enrique A. Mesri, W. Michael Kuehl, and P. Leif Bergsagel From the Department of Medicine, Division of Hematology-Oncology, New York Presbyterian Hospital-Weill Medical College of Cornell University; the Immunology Program, Weill Graduate School of Medical Sciences of Cornell University, New York, NY; and the Genetics Department, Medicine Branch, National Cancer Institute, Bethesda, MD. The t(4;14) translocation occurs frequently in multiple myeloma (MM) and results in the simultaneous dysregulated expression of 2 potential oncogenes, FGFR3 (fibroblast growth factor receptor 3) from der(14) and multiple myeloma SET domain protein/Wolf-Hirschhorn syndrome candidate gene 1 from der(4). It is now shown that myeloma cells carrying a t(4;14) translocation express a functional FGFR3 that in some cases is constitutively activated by the same mutations that cause thanatophoric dysplasia. As with activating mutations of K-ras and N-ras, which are reported in approximately 40% of patients with MM, activating mutations of FGFR3 occur during tumor progression. However, the constitutive activation of ras and FGFR3 does not occur in the same myeloma cells. Thus the activated forms of these proteins appear to share an overlapping role in tumor progression, suggesting that they also share the signaling cascade. Consistent with this prediction, it is shown that activated FGFR3when expressed at levels similar to those seen in t(4;14) myelomais an oncogene that acts through the MAP kinase pathway to transform NIH 3T3 cells, which can then generate tumors in nude mice. Thus, FGFR3, when overexpressed in MM, may be not only oncogenic when stimulated by FGF ligands in the bone marrow microenvironment, but is also a target for activating mutations that enable FGFR3 to play a ras-like role in tumor progression. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: The t(4;14)(p16.3;q32) is strongly associated with chromosome 13 abnormalities in both multiple myeloma and monoclonal gammopathy of undetermined significance Rafael Fonseca, Martin M. Oken, and Philip R. Greipp Blood 2001 98: 1271-1272. [Full Text] [PDF] This article has been cited by other articles: S. Ota, Z.-Q. Zhou, J. M. 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