Melanoma is a skin cancer associated with overexposure to the Sun, but the precise mutagenic event involved in the development of the malignancy has remained unclear. In 9 June Advanced Online Nature, Helen Davies and colleagues of the Cancer Genome Project at the Wellcome Trust Sanger Institute, Cambridge, UK and the Institute of Cancer Research, Surrey, UK show that malignant melanomas have a high frequency of BRAF somatic missense mutations (Nature 2002, DOI:10.1038/nature00766).

Davies et al. screened human cancer cell samples for mutations in the RAS–RAF–MEK–ERK–MAP kinase pathway, which mediates cellular responses to growth signals. They observed BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of other cancers. All mutations were within the kinase domain, with a single substitution (V599E) accounting for 80% of these.

In addition, they show that mutated BRAF proteins have elevated kinase...