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Mutations of the BRAF gene in human cancer.

Publication ,  Journal Article
Davies, H; Bignell, GR; Cox, C; Stephens, P; Edkins, S; Clegg, S; Teague, J; Woffendin, H; Garnett, MJ; Bottomley, W; Davis, N; Dicks, E ...
Published in: Nature
June 27, 2002

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma.

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Published In

Nature

DOI

ISSN

0028-0836

Publication Date

June 27, 2002

Volume

417

Issue

6892

Start / End Page

949 / 954

Location

England

Related Subject Headings

  • ras Proteins
  • Tumor Cells, Cultured
  • Proto-Oncogene Proteins c-raf
  • Proto-Oncogene Proteins B-raf
  • Protein Structure, Tertiary
  • Neoplasms
  • Mutation, Missense
  • Molecular Sequence Data
  • Mitogen-Activated Protein Kinases
  • Mice
 

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Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., … Futreal, P. A. (2002). Mutations of the BRAF gene in human cancer. Nature, 417(6892), 949–954. https://doi.org/10.1038/nature00766
Davies, Helen, Graham R. Bignell, Charles Cox, Philip Stephens, Sarah Edkins, Sheila Clegg, Jon Teague, et al. “Mutations of the BRAF gene in human cancer.Nature 417, no. 6892 (June 27, 2002): 949–54. https://doi.org/10.1038/nature00766.
Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002 Jun 27;417(6892):949–54.
Davies, Helen, et al. “Mutations of the BRAF gene in human cancer.Nature, vol. 417, no. 6892, June 2002, pp. 949–54. Pubmed, doi:10.1038/nature00766.
Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JWC, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA. Mutations of the BRAF gene in human cancer. Nature. 2002 Jun 27;417(6892):949–954.
Journal cover image

Published In

Nature

DOI

ISSN

0028-0836

Publication Date

June 27, 2002

Volume

417

Issue

6892

Start / End Page

949 / 954

Location

England

Related Subject Headings

  • ras Proteins
  • Tumor Cells, Cultured
  • Proto-Oncogene Proteins c-raf
  • Proto-Oncogene Proteins B-raf
  • Protein Structure, Tertiary
  • Neoplasms
  • Mutation, Missense
  • Molecular Sequence Data
  • Mitogen-Activated Protein Kinases
  • Mice