1. ¹Department of Ophthalmology, Leiden University Medical Centre, PO Box 9600, 2300 RC, Leiden, The Netherlands
2. ²Department of Dermatology, Leiden University Medical Centre, Wassenaarseweg 72, 2333 AL, Leiden, The Netherlands
3. ³Queensland Institute of Medical Research, 300 Herston Rd, Herston, QLD 4029, Australia

Correspondence: Dr NA Gruis, E-mail: gruis@lumc.nl

Received 1 December 2004; Revised 10 March 2005; Accepted 24 March 2005; Published online   .

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.