Mutations of the BRAF gene in human cancer

Article English OPEN
Davies, H.; Bignell, G.R.; Cox, C.; Stephens, P.; Edkins, S.; Clegg, S.; Teague, J.; Woffendin, H.; Garnett, M.J.; 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, B.A.; Cooper, C.; Shipley, J.; ... view all 52 authors
(2002)
  • Publisher: Nature Publications Group
  • Subject: RC0254 | RB

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 pathw... View more
  • References (25)
    25 references, page 1 of 3

    Allele Transformed foci per mg DNA Fold increase over wild-type BRAF ............................................................................................................................................................................. WTBRAF 1.3 - V599E 180 138 £ DAVE 0 - L596V 90 70 £ DALV 0 - G463V 130 100 £ GG1426VH8ARAS 129,0000 9,62900££ ............................................................................................................................................................................. NIH3T3 cells were transfected as described in Methods. Transformed foci contained cells like Rasor Raf1-transformed cells-which are refractile and frequently bipolar-and often contained the giant cells typical of RAS or RAF1 transformation. DAVE and DALV are kinase-inactive versions of V599E and L596V, respectively, in which D593 of the conserved DFG motif is replaced by alanine to generate a kinase-dead variant.

    1. Peyssonnaux, C. & Eyche`ne, A. The Raf/MEK/ERK pathway: new concepts of activation. Biol. Cell 93, 53-62 (2001).

    2. Avruch, J. A. et al. Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinase cascade. Recent Prog. Horm. Res. 56, 127-155 (2001).

    3. Kolch, W. Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions. Biochem. J. 351, 289-305 (2000).

    4. Vogelstein, B. et al. Genetic alterations during colorectal-tumour development. N. Engl. J. Med. 319, 525-532 (1988).

    5. van't Veer, L. J. et al. N-ras mutations in human cutaneous melanoma from sun-exposed body sites. Mol. Cell Biol. 9, 3114-3116 (1989).

    6. Caduff, R. F., Svoboda-Newman, S. M., Ferguson, A. W., Johnston, C. M. & Frank, T. S. Comparison of mutations of Ki-RAS and p53 immunoreactivity in borderline and malignant epithelial ovarian tumours. Am. J. Surg. Pathol. 23, 323-328 (1999).

    7. Daya-Grosjean, L., Dumaz, N. & Sarasin, A. The specificity of p53 mutation spectra in sunlight induced human cancers. J. Photochem. Photobiol. B 28, 115-124 (1995).

    8. Halaban, R. The regulation of normal melancyte proliferation. Pigment Cell Res. 13, 4-14 (2000).

    9. Busca, R. et al. Ras mediates the cAMP-dependent activation of extracellular signal-regulated kinases (ERKs) in melanocytes. EMBO J. 19, 2900-2910 (2000).

  • Related Organizations (20)
  • Metrics
Share - Bookmark