title: Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS.
abstract: In contrast to cutaneous melanoma, there is no evidence that BRAF mutations are involved in the activation of the mitogen-activated protein kinase (MAPK) pathway in uveal melanoma, although there is increasing evidence that this pathway is activated frequently in the latter tumours. In this study, we performed mutation analysis of the RAS and BRAF genes in a panel of 11 uveal melanoma cell lines and 19 primary uveal melanoma tumours. In addition, Western blot and immunohistochemical analyses were performed on downstream members of the MAPK pathway in order to assess the contribution of each of these components. No mutations were found in any of the three RAS gene family members and only one cell line carried a BRAF mutation (V599E). Despite this, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), ERK and ELK were constitutively activated in all samples. These data suggest that activation of the MAPK pathway is commonly involved in the development of uveal melanoma, but occurs through a mechanism different to that of cutaneous melanoma.
authors.affiliation: Department of Ophthalmology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Zuidervaart
authors.forename: F
authors.initials: F
authors.lastname: van Nieuwpoort
authors.forename: M
authors.initials: M
authors.lastname: Stark
authors.forename: R
authors.initials: R
authors.lastname: Dijkman
authors.forename: L
authors.initials: L
authors.lastname: Packer
authors.forename: A-M
authors.initials: AM
authors.lastname: Borgstein
authors.forename: S
authors.initials: S
authors.lastname: Pavey
authors.forename: P
authors.initials: P
authors.lastname: van der Velden
authors.forename: C
authors.initials: C
authors.lastname: Out
authors.forename: M J
authors.initials: MJ
authors.lastname: Jager
authors.forename: N K
authors.initials: NK
authors.lastname: Hayward
authors.forename: N A
authors.initials: NA
authors.lastname: Gruis
mesh_terms: D015153:Blotting, Western; D004252:DNA Mutational Analysis; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D048493:Proto-Oncogene Proteins B-raf / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D048493:Proto-Oncogene Proteins B-raf; D020928:Mitogen-Activated Protein Kinases