Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-26T07:10:53.509Z Has data issue: false hasContentIssue false

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

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

1Naumann, U., Eisenmann-Tappe, I. and Rapp, U.R. (1997) The role of Raf kinases in development and growth of tumors. Recent Results Cancer Res 143, 237-244CrossRefGoogle ScholarPubMed
2Beeram, M., Patnaik, A. and Rowinsky, E.K. (2005) Raf: a strategic target for therapeutic development against cancer. J Clin Oncol 23, 6771-6790CrossRefGoogle ScholarPubMed
3Emuss, V. et al. (2005) Mutations of C-RAF are rare in human cancer because C-RAF has a low basal kinase activity compared with B-RAF. Cancer Res 65, 9719-9726CrossRefGoogle Scholar
4Pritchard, C.A. et al. (1995) Conditionally oncogenic forms of the A-Raf and B-Raf protein kinases display different biological and biochemical properties in NIH 3T3 cells. Mol Cell Biol 15, 6430-6442CrossRefGoogle ScholarPubMed
5Peyssonnaux, C. and Eychène, A. (2001) The Raf/MEK/ERK pathway: new concepts of activation. Biol Cell 93, 53-62CrossRefGoogle ScholarPubMed
6Cruz, F. 3rd et al. (2003) Absence of BRAF and NRAS mutations in uveal melanoma. Cancer Res 63, 5761-5766Google ScholarPubMed
7Marshall, C.J. (1994) MAP kinase kinase kinase, MAP kinase kinase and MAP kinase. Curr Opin Genet Dev 4, 82-89CrossRefGoogle ScholarPubMed
8Kohno, M. and Pouyssegur, J. (2006) Targeting the ERK signaling pathway in cancer therapy. Ann Med 38, 200-211CrossRefGoogle ScholarPubMed
9Domingo, E. and Schwartz, S. Jr. (2004) BRAF. In Atlas of Genetics and Cytogenetics in Oncology and Haematology. http://AtlasGeneticsOncology.org/Genes/BRAFID828.htmlGoogle Scholar
10Davies, H. et al. (2002) Mutations of the BRAF gene in human cancer. Nature 417, 949-954CrossRefGoogle ScholarPubMed
11Edlundh-Rose, E. et al. (2006) NRAS and BRAF mutations in melanoma tumours in relation to clinical characteristics: a study based on mutation screening by pyrosequencing. Melanoma Res 16, 471-478CrossRefGoogle ScholarPubMed
12Cohen, Y. et al. (2003) BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst 95, 625-627CrossRefGoogle ScholarPubMed
13Rajagopalan, H. et al. (2002) RAF/RAS oncogenes and mismatch-repair status. Nature 418, 934CrossRefGoogle ScholarPubMed
14Singer, G. et al. (2003) Mutations in BRAF and KRAS characterize the development of low- grade ovarian serous carcinoma. J Natl Cancer Inst 95, 484-486CrossRefGoogle ScholarPubMed
15Brose, M.S. et al. (2002) BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res 62, 6997-7000Google ScholarPubMed
16Wan, P.T. et al. (2004) Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 116, 855-867CrossRefGoogle ScholarPubMed
17Jackson, S. et al. (2005) No evidence for BRAF as a melanoma/nevus susceptibility gene. Cancer Epidemiol Biomarkers Prev 14, 913-918CrossRefGoogle ScholarPubMed
18Meyer, P. (2003) Exclusion of BRAFV599E as a melanoma susceptibility mutation. Int J Cancer 106, 78-80CrossRefGoogle ScholarPubMed
19Laud, K. et al. (2003) BRAF as a melanoma susceptibility candidate gene? Cancer Res 63, 3061-3065Google ScholarPubMed
20Lang, J., Boxer, M. and MacKie, R. (2003) Absence of exon 15 BRAF germline mutations in familial melanoma. Hum Mutat 21, 327-330CrossRefGoogle ScholarPubMed
21Casula, M. et al. (2004) BRAF gene is somatically mutated but does not make a major contribution to malignant melanoma susceptibility: the Italian Melanoma Intergroup Study. J Clin Oncol 22, 286-292CrossRefGoogle ScholarPubMed
22Wellbrock, C. et al. (2004) V599EB-RAF is an oncogene in melanocytes. Cancer Res 64, 2338-2342CrossRefGoogle ScholarPubMed
23Bennett, D.C., Cooper, P.J. and Hart, I.R. (1987) A line of non-tumorigenic mouse melanocytes, syngeneic with the B16 melanoma and requiring a tumour promoter for growth. Int J Cancer 39, 414-418CrossRefGoogle ScholarPubMed
24Hingorani, S.R. et al. (2003) Suppression of BRAF (V599E) in human melanoma abrogates transformation. Cancer Res 63, 5198-5202Google ScholarPubMed
25Chudnovsky, Y. et al. (2005) Use of human tissue to assess the oncogenic activity of melanoma-associated mutations. Nat Genet 37, 745-749CrossRefGoogle ScholarPubMed
26Uribe, P., Wistuba, I.I. and Gonzalez, S. (2003) BRAF mutation: a frequent event in benign, atypical, and malignant melanocytic lesions of the skin. Am J Dermatopathol 25, 365-370CrossRefGoogle ScholarPubMed
27Pollock, P.M. et al. (2003) High frequency of BRAF mutations in nevi. Nat Genet 33, 19-20CrossRefGoogle ScholarPubMed
28Poynter, J. et al. (2006) BRAF and NRAS mutations in melanoma and melanocytic nevi. Melanoma Res 16, 267-273CrossRefGoogle ScholarPubMed
29Hoeflich, K.P. et al. (2006) Oncogenic BRAF is required for tumor growth and maintenance in melanoma models. Cancer Res 66, 999-1006CrossRefGoogle ScholarPubMed
30Loewe, R. et al. (2004) BRAF kinase gene V599E mutation in growing melanocytic lesions. J Invest Dermatol 123, 733-736CrossRefGoogle ScholarPubMed
31Yazdi, A.S. et al. (2003) Mutations of the BRAF gene in benign and malignant melanocytic lesions. J Invest Dermatol 121, 1160-1162CrossRefGoogle ScholarPubMed
32Bevona, C. et al. (2003) Cutaneous melanomas associated with nevi. Arch Dermatol 139, 1620-1624CrossRefGoogle ScholarPubMed
33Kuwata, T., Kitagawa, M. and Kasuga, T. (1993) Proliferative activity of primary cutaneous melanocytic tumours. Virchows Arch A Pathol Anat Histopathol 423, 359-364CrossRefGoogle ScholarPubMed
34Chin, L., Merlino, G. and DePinho, R.A. (1998) Malignant melanoma: modern black plague and genetic black box. Genes Dev 12, 3467-3481CrossRefGoogle ScholarPubMed
35Michaloglou, C. et al. (2005) BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436, 720-724CrossRefGoogle ScholarPubMed
36Bennett, D.C. (2003) Human melanocyte senescence and melanoma susceptibility genes. Oncogene 22, 3063-3069CrossRefGoogle ScholarPubMed
37Dong, J. et al. (2003) BRAF oncogenic mutations correlate with progression rather than initiation of human melanoma. Cancer Res 63, 3883-3885Google ScholarPubMed
38Curtin, J.A. et al. (2005) Distinct sets of genetic alterations in melanoma. New Engl J Med 353, 2135-2147CrossRefGoogle ScholarPubMed
39Shinozaki, M. et al. (2004) Incidence of BRAF oncogene mutation and clinical relevance for primary cutaneous melanomas. Clin Cancer Res 10, 1753-1757CrossRefGoogle ScholarPubMed
40Daniotti, M. et al. (2007) Detection of mutated BRAFV600E variant in circulating DNA of stage III-IV melanoma patients. Int J Cancer 120, 2439-2444CrossRefGoogle ScholarPubMed
41Curtin, J.A. et al. (2006) Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol 24, 4340-4346CrossRefGoogle ScholarPubMed
42Libra, M. et al. (2006) Absence of BRAF gene mutation in non-melanoma skin tumors. Cell Cycle 968-970CrossRefGoogle ScholarPubMed
43Albino, A.P. et al. (1989) Analysis of ras oncogenes in malignant melanoma and precursor lesions: Correlation of point mutations with differentiation phenotype. Oncogene 4, 1363-1374Google ScholarPubMed
44Hocker, T., and Tsao, H. (2007) Ultraviolet radiation and melanoma: a systematic review and analysis of reported sequence variants. Hum Mutat 28, 578-588CrossRefGoogle ScholarPubMed
45Bauer, J. et al. (2007) Congenital melanocytic nevi frequently harbor NRAS mutations but no BRAF mutations. J Invest Dermatol 127, 179-182CrossRefGoogle ScholarPubMed
46Balch, C.M. (1992) Cutaneous melanoma: prognosis and treatment results worldwide. Semin Surg Oncol 8, 400-414CrossRefGoogle ScholarPubMed
47Jhappan, C., Noonan, F.P. and Merlino, G. (2003) Ultraviolet radiation and cutaneous malignant melanoma. Oncogene 22, 3099-3112CrossRefGoogle ScholarPubMed
48Thomas, N.E., Berwick, M. and Cordeiro-Stone, M. (2006) Could BRAF mutations in melanocytic lesions arise from dna damage induced by ultraviolet radiation? J Invest Dermatol 126, 1693-1696CrossRefGoogle ScholarPubMed
49Zuidervaart, W. et al. (2005) Activation of the MAPK pathway is a common even in uveal melanomas although it rarely occurs through mutation of BRAF or RAS. Br J Cancer 92, 2032-2038CrossRefGoogle ScholarPubMed
50Edmunds, S.C. et al. (2003) Absence of BRAF gene mutations in uveal melanomas in contrast to cutaneous melanomas. Br J Cancer 88, 1403-1405CrossRefGoogle ScholarPubMed
51Cohen, Y. et al. (2003) Lack of BRAF mutation in primary uveal melanoma. Invest Ophthalmol Vis Sci 44, 2876-2878CrossRefGoogle ScholarPubMed
52Rimoldi, D. et al. (2003) Lack of BRAF mutations in uveal melanoma. Cancer Res 63, 5712-5715Google ScholarPubMed
53Weber, A. et al. (2003) Absence of mutations of the BRAF gene and constitutive activation of extracellular-regulated kinase in malignant melanomas of the uvea. Lab Invest 683, 1771-1776CrossRefGoogle Scholar
54Landi, M.T. et al. (2006) MC1R germline variants confer risk for BRAF-mutant melanoma. Science 313, 521-522CrossRefGoogle ScholarPubMed
55Rees, J.L. (2004) The genetics of sun sensitivity in humans. Am J Hum Genet 75, 739-751CrossRefGoogle ScholarPubMed
56Fargnoli, M.C. et al. (2006) MC1R, ASIP, and DNA Repair in Sporadic and Familial Melanoma in a Mediterranean Population. J Natl Cancer Inst 98, 144-145CrossRefGoogle Scholar
57Kennedy, C. et al. (2001) Melanocortin 1 Receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color. J Invest Dermatol 117, 294-300CrossRefGoogle ScholarPubMed
58Palmer, J.S. et al. (2000) Melanocortin-1 receptor polymorphisms and risk of melanoma: is the association explained solely by pigmentation phenotype? Am J Hum Genet 66, 176-186CrossRefGoogle ScholarPubMed
59Li, L. et al. (2006) Uveal melanocytes do not respond to or express receptors for alpha-melanocyte-stimulating hormone. Invest Ophthalmol Vis Sci 47, 4507-4512CrossRefGoogle ScholarPubMed
60Liu, W. et al. (2007) Distinct clinical and pathological features are associated with the BRAFT1799A (V600E) mutation in primary melanoma. J Invest Dermatol 127, 900-905CrossRefGoogle ScholarPubMed
61 (2004) The American Heritage Stedman's Medical Dictionary (2nd edn), Houghton MifflinGoogle Scholar
62Kumar, R. et al. (2003) BRAF mutations in metastatic melanoma, A possible association with clinical outcome. Clin Cancer Res 9, 3362-3368Google ScholarPubMed
63Adnane, L. et al. (2005) Sorafenib (BAY 43-9006, Nexavar®), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. Methods Enzymol 407, 597-612CrossRefGoogle Scholar
64Strumberg, D. (2005) Preclinical and clinical development of the oral multikinase inhibitor sorafenib in cancer treatment. Drugs Today 41, 773-784CrossRefGoogle ScholarPubMed
65Murphy, D.A. et al. (2006) Inhibition of tumor endothelial ERK activation, angiogenesis, and tumor growth by sorafenib (BAY43-9006). Am J Pathol 169, 1875-1885CrossRefGoogle ScholarPubMed
66Karasarides, M. et al. (2004) B-RAF is a therapeutic target in melanoma. Oncogene 23, 6292-6298CrossRefGoogle ScholarPubMed
67Strumberg, D. et al. (2006) Pooled safety analysis of BAY 43-9006 (sorafenib) monotherapy in patients with advanced solid tumours: Is rash associated with treatment outcome? Eur J Cancer 42, 548-556CrossRefGoogle ScholarPubMed
68Eisen, T. et al. (2006) Sorafenib in advanced melanoma: A phase II randomised discontinuation trial analysis. Br J Cancer 95, 581-586CrossRefGoogle ScholarPubMed
69Flaherty, K.T. et al. (2004) Phase I/II trial of BAY 43-9006, carboplatin (C) and paclitaxel (P) demonstrates preliminary antitumor activity in the expansion cohort of patients with metastatic melanoma. J Clin Oncol ASCO Ann Meeting Proc Suppl 22, 7507Google Scholar
70Amaravadi, R.K. et al. (2006) Preliminary results of a randomized phase II study comparing two schedules of temozolomide in combination with sorafenib in patients with advanced melanoma. J Clin Oncol ASCO Ann Meeting Proc Suppl 24, 8009Google Scholar
71King, A.J. et al. (2006) Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885. Cancer Res 66, 11100-11105CrossRefGoogle ScholarPubMed
72Eisen, T. et al. (2006) Randomized Phase III trial of Sorafenib in advanced renal cell carcinoma (rcc): impact of crossover on survival. J Clin Oncol ASCO Ann Meeting Proc Suppl 24, 4524Google Scholar
73Escudier, B. et al. (2005) Randomized Phase III trial of the Raf kinase and VEGFR inhibitor Sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC). J Clin Oncol ASCO Ann Meeting Proc Suppl 23, 4510Google Scholar
74Neckers, L. and Neckers, K. (2005) Heat-shock protein 90 inhibitors as novel cancer chemotherapeutics—an update. Expert Opin Emerg Drugs 10, 137-149CrossRefGoogle ScholarPubMed
75Maloney, A. and Workman, P. (2002) HSP90 as a new therapeutic target for cancer therapy: the story unfolds. Expert Opin Biol Ther 2, 3-24CrossRefGoogle ScholarPubMed
76da RochaDias, S. Dias, S. et al. (2005) Activated B-RAF is an Hsp90 client protein that is targeted by the anticancer drug 17-allylamino-17-demethoxygeldanamycin. Cancer Res 65, 10686-10691CrossRefGoogle Scholar
77Daniotti, M. et al. (2004) BRAF alterations are associated with complex mutational profiles in malignant melanoma. Oncogene 23, 5968-5977CrossRefGoogle ScholarPubMed
78Haqq, C. et al. (2005) The gene expression signatures of melanoma progression. Proc Natl Acad Sci U S A 102, 6092-6097CrossRefGoogle ScholarPubMed
79Bittner, M. et al. (2000) Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature 406, 536-540CrossRefGoogle ScholarPubMed
80Seftor, E.A. et al. (2002) Molecular determinants of human uveal melanoma invasion and metastasis. Clin Exp Metastasis 19, 233-246CrossRefGoogle ScholarPubMed
81de Wit, N.J. et al. (2002) Differentially expressed genes identified in human melanoma cell lines with different metastatic behaviour using high density oligonucleotide arrays. Melanoma Res 12, 57-69CrossRefGoogle ScholarPubMed
82Bloethner, S. et al. (2005) Effect of common B-RAF and N-RAS mutations on global gene expression in melanoma cell lines. Carcinogenesis 26, 1224-1232CrossRefGoogle ScholarPubMed
83Pavey, S. et al. (2004) Microarray expression profiling in melanoma reveals a BRAF mutation signature. Oncogene 23, 4060-4067CrossRefGoogle ScholarPubMed
84Hoek, K.S. et al. (2006) Metastatic potential of melanomas defined by specific gene expression profiles with no BRAF signature. Pigment Cell Res 19, 290-302CrossRefGoogle ScholarPubMed
85Jonsson, G. et al. (2007) Genomic profiling of malignant melanoma using tiling-resolution arrayCGH. Oncogene 26, 4738-4748CrossRefGoogle ScholarPubMed
86Barnhill, R.L. et al. (1996) Predicting five-year outcome for patients with cutaneous melanoma in a population-based study. Cancer 78, 427-4323.0.CO;2-G>CrossRefGoogle ScholarPubMed
87Thomas, N.E. et al. (2004) Tandem BRAF mutations in primary invasive melanomas. J Invest Dermatol 122, 1245-1250CrossRefGoogle ScholarPubMed
88Reifenberger, J. et al. (2004) Frequent alterations of Ras signaling pathway genes in sporadic malignant melanomas. Int J Cancer 109, 377-384CrossRefGoogle ScholarPubMed
89Saldanha, G. et al. (2005) Cutaneous melanoma subtypes show different BRAF and NRAS mutation frequencies. Clin Cancer Res 12, 4499-4505CrossRefGoogle Scholar
90Lang, J. and MacKie, R.M. (2005) Prevalence of exon 15 BRAF mutations in primary melanoma of the superficial spreading, nodular, acral, and lentigo maligna subtypes. J Invest Dermatol 125, 575-57CrossRefGoogle ScholarPubMed
91Omholt, K. et al. (2003) NRAS and BRAF mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression. Clin Cancer Res 9, 6483-6488Google ScholarPubMed
92Maldonado, J.L. et al. (2003) Determinants of BRAF mutations in primary melanomas. J Natl Cancer Inst 95, 1878-1890CrossRefGoogle ScholarPubMed
93Davison, J.M. et al. (2005) Absence of V599E BRAF mutations in desmoplastic melanomas. Cancer 103, 788-792CrossRefGoogle ScholarPubMed
94Edwards, R.H. et al. (2004) Absence of BRAF mutations in UV-protected mucosal Melanomas. J Med Genet 41, 270-272CrossRefGoogle ScholarPubMed
95Cunningham, C.C. et al. (2000) Advances in brief: a Phase I trial of c-Raf kinase antisense oligonucleotide ISIS 5132 administered as a continuous intravenous infusion in patients with advanced cancer. Clin Cancer Res 6, 1626-1531Google Scholar
96King, A.J. et al. (2006) Demonstration of a genetic therapeutic index for tumors oncogenic BRAF by the kinase inhibitor SB-590885. Cancer Res 66, 11100-11105CrossRefGoogle ScholarPubMed

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