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RAF/RAS oncogenes and mismatch-repair status

Author

Listed:
  • Harith Rajagopalan

    (Sidney Kimmel Comprehensive Cancer Center, Howard Hughes Medical Institute, and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine)

  • Alberto Bardelli

    (Sidney Kimmel Comprehensive Cancer Center, Howard Hughes Medical Institute, and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine)

  • Christoph Lengauer

    (Sidney Kimmel Comprehensive Cancer Center, Howard Hughes Medical Institute, and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine)

  • Kenneth W. Kinzler

    (Sidney Kimmel Comprehensive Cancer Center, Howard Hughes Medical Institute, and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine)

  • Bert Vogelstein

    (Sidney Kimmel Comprehensive Cancer Center, Howard Hughes Medical Institute, and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine)

  • Victor E. Velculescu

    (Sidney Kimmel Comprehensive Cancer Center, Howard Hughes Medical Institute, and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine)

Abstract

Genes of the RAF family encode kinases that are regulated by Ras and mediate cellular responses to growth signals. Activating mutations in one RAF gene, BRAF, have been found in a high proportion of melanomas and in a small fraction of other cancers1. Here we show that BRAF mutations in colorectal cancers occur only in tumours that do not carry mutations in a RAS gene known as KRAS, and that BRAF mutation is linked to the proficiency of these tumours in repairing mismatched bases in DNA. Our results not only provide genetic support for the idea that mutations in BRAF and KRAS exert equivalent effects in tumorigenesis2, but also emphasize the role of repair processes in establishing the mutation spectra that underpin human cancer.

Suggested Citation

  • Harith Rajagopalan & Alberto Bardelli & Christoph Lengauer & Kenneth W. Kinzler & Bert Vogelstein & Victor E. Velculescu, 2002. "RAF/RAS oncogenes and mismatch-repair status," Nature, Nature, vol. 418(6901), pages 934-934, August.
    • Handle: RePEc:nat:nature:v:418:y:2002:i:6901:d:10.1038_418934a
    DOI: 10.1038/418934a
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