title: Lack of BRAF mutations in uveal melanoma.
abstract: RAF proteins are serine/threonine kinases that mediate cellular responses to growth signals by activating the mitogen-activated protein kinase pathway. Mutations in the BRAF gene causing a V599E amino acid substitution that enhance the kinase activity have been described in >60% of cutaneous melanomas and premalignant melanocytic lesions. We have investigated the frequency of BRAF mutations at the expression level in melanomas of the uveal tract. None of the 30 metastases and 10 primary uveal melanomas tested expressed the V599E mutation. In contrast, this mutation was expressed by 65% of cutaneous melanoma samples, confirming previous results. In addition, a double mutation resulting in V599K substitution was detected in two suspect ocular metastases of cutaneous melanoma. Analysis of exon 11, the second common site of BRAF mutations, revealed only wild-type sequences in uveal melanomas. Analysis of tumor lysates showed the presence of phosphorylated mitogen-activated protein kinase, kinase, and mitogen-activated protein kinase in 50% of uveal and 100% of cutaneous melanoma metastases. Taken together, these results suggest that although the common BRAF mutations found in cutaneous melanoma do not play a role in tumorigenesis of uveal tract melanocytes, activation of the RAF/mitogen-activated protein kinase pathway may nevertheless play an important role in uveal melanoma.
authors.affiliation: Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Switzerland. Donata.Rimoldi@isrec.unil.ch
authors.forename: Donata
authors.initials: D
authors.lastname: Rimoldi
authors.forename: Suzanne
authors.initials: S
authors.lastname: Salvi
authors.forename: Danielle
authors.initials: D
authors.lastname: Liénard
authors.forename: Ferdy J
authors.initials: FJ
authors.lastname: Lejeune
authors.forename: Daniel
authors.initials: D
authors.lastname: Speiser
authors.forename: Leonidas
authors.initials: L
authors.lastname: Zografos
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Cerottini
mesh_terms: D005091:Exons / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism; D014604:Uveal Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D015513:Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf