The RAS-BRAF kinase pathway is not involved in uveal melanoma.

An activating mutation has been recently observed in cutaneous melanoma in a downstream component of RAS-BRAF. The most common mutation, occurring in 80% of cutaneous melanoma samples, is a T-to-A transition resulting in a single amino acid substitution (V599E). Since cutaneous and uveal melanoma (UM) have a common origin, we aimed to establish whether activation of the BRAF proto-oncogene is also an important factor in the development of UM. Exons 11 through 18 of the BRAF gene were screened from 33 primary UMs and 11 UM cell lines. Genomic polymerase chain reaction products were evaluated using single-strand conformation polymorphism analysis, followed by sequencing of aberrant products. The most common mutation, T1796A in the kinase domain of BRAF, was not observed in any of the primary UM samples. This mutation was also absent in 10 of the 11 UM cell lines. In one of the UM cell lines, OCM1, the T1796A mutation was present. We conclude that, in contrast to cutaneous melanoma, BRAF does not appear to be involved in the pathogenesis of UM.