STUDY: Mutations of the BRAF gene in human cancer

JOURNAL: Nature:10.1038/nature00766

AUTHORS: HELEN DAVIES et al.

ABSTRACT: Sixty-six per cent of malignant melanomas have mutations in the BRAF gene. The same gene is also mutated in a smaller proportion of a wide range of other human cancers.

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COMMENTARY: The discovery "may provide new therapeutic opportunities in malignant melanoma.

The discovery has emerged from the first stage of a systematic genome-wide search for the genes that often accrue cancer-causing mutations - those that alter normal programmes of cell proliferation, differentiation and death.

The mutations were initially identified by comparing the BRAF sequence from 15 cancerous cell lines with that from healthy cells from the same donors. Similar mutations were then found in numerous other cancer cell lines and in a high proportion of the 378 primary human cancer samples screened. Most of the mutations are at a very specific location in the BRAF gene.

They disrupt the enzymatic activity of the BRAF protein and hence the growth of an affected cell. The researchers focussed on BRAF as it is biochemically linked to a central cellular growth control pathway on which several other important human oncogenes have been found.