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E. Kilic, H.T. Brüggenwirth, C.M. Mooy, M. Verbiest, A. de Klein; Involvement of B-Raf in Uveal Melanoma Development . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1541.
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Purpose: The Ras-Raf-Mek-Erk pathway mediates cellular responses to growth signals. Two components of this pathway, Ras and Raf, are protooncogenes. Ras is mutated in many types of cancer, e.g. malignant melanoma of the skin, but not in Uveal Melanoma (UM). In malignant melanoma, it is reported that the downstream component of Ras, B-Raf is mutated in the absence of Ras mutations. Therefore, we established whether the B-Raf protooncogene is also an important factor in the development of UM. Methods: In 33 primary tumors and 11 UM cell lines the kinase domain of B-Raf was screened. Genomic PCR products were analyzed using SSCP analysis followed by sequencing in case of an aberrant product. Results: The common mutation in cutaneous melanoma of the kinase domain of B-Raf (V599E) was not observed in any of the primary uveal melanomas. However, this mutation was present in one of the UM cell lines and the control skin melanoma and colon carcinoma cell lines. In this study two other possible polymorfic nucleotide changes resulting in an amino acid substitution were found.
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