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BRAF kinase in melanoma development and progression

Published online by Cambridge University Press:  18 February 2008

Amena M. DeLuca
Affiliation:
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Archana Srinivas
Affiliation:
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rhoda M. Alani*
Affiliation:
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
*
*Corresponding author: Rhoda M. Alani, Laboratory of Cutaneous Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, CRB 1, Suite 344, Baltimore, MD 21231-1000, USA. Tel: +1 410 614 6204; Fax: +1 410 614 5015; E-mail: [email protected]

Abstract

Cutaneous melanoma is increasing in incidence at one of the highest rates for any form of cancer in the USA, with a current lifetime incidence of 1 in 68. Although early-stage disease is often curable, the survival rate for advanced disease is low, with an average life expectancy of 6–10 months. Knowledge of the molecular alterations associated with melanoma development and progression is expected to lead to improved therapies and outcomes. Major progress in defining the molecular alterations associated with the evolution of melanoma came in 2002, through a systematic genome-wide assessment of cancer-associated pathways. Large-scale sequencing of growth-associated genes in a variety of cancers identified a high frequency (>60%) of activating mutations of the BRAF kinase gene in human melanomas. This discovery has prompted a large number of studies evaluating the biological significance of BRAF kinase mutations in the initiation and progression of melanoma, and their importance for the development of novel melanoma therapies. Here we review the most recent studies of BRAF kinase in the pathogenesis of melanoma and their implications for defining BRAF kinase as a therapeutic point of interest in melanoma.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2008

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References

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Further reading, resources and contacts

National Cancer Institute site for melanoma:

Davies, H. et al. (2002) Mutations of the BRAF gene in human cancer. Nature 417, 949-954CrossRefGoogle ScholarPubMed
Pollock, P.M. et al. (2003) High frequency of BRAF mutations in nevi. Nat Genet 33, 19-20CrossRefGoogle ScholarPubMed
Curtin, J.A. et al. (2005) Distinct sets of genetic alterations in melanoma. New Engl J Med 353, 2135-2145CrossRefGoogle ScholarPubMed
Balch, C.M. et al. (2006) Cutaneous Melanoma (4th edn), Quality Medical Publishing, St Louis, MO, USAGoogle Scholar
Nordlund, J.J. et al. , eds (2006) The Pigmentary System: Physiology and Pathophysiology (2nd edn), Blackwell, Oxford, UKCrossRefGoogle Scholar
Davies, H. et al. (2002) Mutations of the BRAF gene in human cancer. Nature 417, 949-954CrossRefGoogle ScholarPubMed
Pollock, P.M. et al. (2003) High frequency of BRAF mutations in nevi. Nat Genet 33, 19-20CrossRefGoogle ScholarPubMed
Curtin, J.A. et al. (2005) Distinct sets of genetic alterations in melanoma. New Engl J Med 353, 2135-2145CrossRefGoogle ScholarPubMed
Balch, C.M. et al. (2006) Cutaneous Melanoma (4th edn), Quality Medical Publishing, St Louis, MO, USAGoogle Scholar
Nordlund, J.J. et al. , eds (2006) The Pigmentary System: Physiology and Pathophysiology (2nd edn), Blackwell, Oxford, UKCrossRefGoogle Scholar