New insight into BRAF mutations in cancer

Current Opinion in Genetics and Development

Volumn 17, Issue 1, 2007, Pages 31-39

  Dhomen, Nathalie ^a   Marais, Richard ^a  

^a IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

B RAF KINASE; MELANOCORTIN 1 RECEPTOR;

CANCER; CANCER GENETICS; GENE LOCUS; GENE MUTATION; GENETIC SUSCEPTIBILITY; HUMAN; MELANOMA; NONHUMAN; ONCOGENE RAS; PRIORITY JOURNAL; REVIEW;

GENE REGULATORY NETWORKS; HUMANS; MELANOMA; MUTATION; PROTO-ONCOGENE PROTEINS B-RAF; RECEPTOR, MELANOCORTIN, TYPE 1; SIGNAL TRANSDUCTION; ULTRAVIOLET RAYS;

EID: 33846201272     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.gde.2006.12.005     Document Type: Review

References (74)

1. Pritchard C.A., Samuels M.L., Bosch E., and McMahon M. 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 (1995) 6430-6442
2. Wojnowski L., Zimmer A.M., Beck T.W., Hahn H., Bernal R., Rapp U.R., and Zimmer A. Endothelial apoptosis in Braf-deficient mice. Nat Genet 16 (1997) 293-297
3. Wojnowski L., Stancato L.F., Zimmer A.M., Hahn H., Beck T.W., Larner A.C., Rapp U.R., and Zimmer A. Craf-1 protein kinase is essential for mouse development. Mech Dev 76 (1998) 141-149
4. Galabova-Kovacs G., Matzen D., Piazzolla D., Meissl K., Plyushch T., Chen A.P., Silva A., and Baccarini M. Essential role of B-Raf in ERK activation during extraembryonic development. Proc Natl Acad Sci USA 103 (2006) 1325-1330
5. Mikula M., Schreiber M., Husak Z., Kucerova L., Ruth J., Wieser R., Zatloukal K., Beug H., Wagner E.F., and Baccarini M. Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene. EMBO J 20 (2001) 1952-1962
6. Huser M., Luckett J., Chiloeches A., Mercer K., Iwobi M., Giblett S., Sun X.M., Brown J., Marais R., and Pritchard C. MEK kinase activity is not necessary for Raf-1 function. EMBO J 20 (2001) 1940-1951
7. Davies H., Bignell G.R., Cox C., Stephens P., Edkins S., Clegg S., Teague J., Woffendin H., Garnett M.J., Bottomley W., et al. Mutations of the BRAF gene in human cancer. Nature 417 (2002) 949-954
8. Garnett M.J., and Marais R. Guilty as charged: B-RAF is a human oncogene. Cancer Cell 6 (2004) 313-319
9. Emuss V., Garnett M., Mason C., and Marais R. 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 (2005) 9719-9726. The authors describe why ARAF and CRAF mutations in cancer are rare. A fundamental difference in regulation of BRAF compared with ARAF and CRAF makes BRAF susceptible to activation by single amino acid changes, whereas ARAF and CRAF require two changes.
10. Zebisch A., Staber P.B., Delavar A., Bodner C., Hiden K., Fischereder K., Janakiraman M., Linkesch W., Auner H.W., Emberger W., et al. Two transforming C-RAF germ-line mutations identified in patients with therapy-related acute myeloid leukemia. Cancer Res 66 (2006) 3401-3408
11. Lee J.W., Soung Y.H., Kim S.Y., Park W.S., Nam S.W., Min W.S., Kim S.H., Lee J.Y., Yoo N.J., and Lee S.H. Mutational analysis of the ARAF gene in human cancers. APMIS 113 (2005) 54-57
12. Satyamoorthy K., Li G., Gerrero M.R., Brose M.S., Volpe P., Weber B.L., Van Belle P., Elder D.E., and Herlyn M. Constitutive mitogen-activated protein kinase activation in melanoma is mediated by both BRAF mutations and autocrine growth factor stimulation. Cancer Res 63 (2003) 756-759
13. Wellbrock C., Ogilvie L., Hedley D., Karasarides M., Martin J., Niculescu-Duvaz D., Springer C.J., and Marais R. V599EB-RAF is an oncogene in melanocytes. Cancer Res 64 (2004) 2338-2342
14. Ikenoue T., Hikiba Y., Kanai F., Tanaka Y., Imamura J., Imamura T., Ohta M., Ijichi H., Tateishi K., Kawakami T., et al. Functional analysis of mutations within the kinase activation segment of B-Raf in human colorectal tumors. Cancer Res 63 (2003) 8132-8137
15. Houben R., Becker J.C., Kappel A., Terheyden P., Brocker E.B., Goetz R., and Rapp U.R. Constitutive activation of the Ras-Raf signaling pathway in metastatic melanoma is associated with poor prognosis. J Carcinog 3 (2004) 6
16. Ikenoue T., Hikiba Y., Kanai F., Aragaki J., Tanaka Y., Imamura J., Imamura T., Ohta M., Ijichi H., Tateishi K., et al. Different effects of point mutations within the B-Raf glycine-rich loop in colorectal tumors on mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase and nuclear factor kappaB pathway and cellular transformation. Cancer Res 64 (2004) 3428-3435
17. Hingorani S.R., Jacobetz M.A., Robertson G.P., Herlyn M., and Tuveson D.A. Suppression of BRAF(V599E) in human melanoma abrogates transformation. Cancer Res 63 (2003) 5198-5202
18. Karasarides M., Chiloeches A., Hayward R., Niculescu-Duvaz D., Scanlon I., Friedlos F., Ogilvie L., Hedley D., Martin J., Marshall C.J., et al. B-RAF is a therapeutic target in melanoma. Oncogene 23 (2004) 6292-6298
19. Hoeflich K.P., Gray D.C., Eby M.T., Tien J.Y., Wong L., Bower J., Gogineni A., Zha J., Cole M.J., Stern H.M., et al. Oncogenic BRAF is required for tumor growth and maintenance in melanoma models. Cancer Res 66 (2006) 999-1006
20. Pollock P.M., Harper U.L., Hansen K.S., Yudt L.M., Stark M., Robbins C.M., Moses T.Y., Hostetter G., Wagner U., Kakareka J., et al. High frequency of BRAF mutations in nevi. Nat Genet 33 (2003) 19-20
21. Yazdi A.S., Palmedo G., Flaig M.J., Puchta U., Reckwerth A., Rutten A., Mentzel T., Hugel H., Hantschke M., Schmid-Wendtner M.H., et al. Mutations of the BRAF gene in benign and malignant melanocytic lesions. J Invest Dermatol 121 (2003) 1160-1162
22. Dong J., Phelps R.G., Qiao R., Yao S., Benard O., Ronai Z., and Aaronson S.A. BRAF oncogenic mutations correlate with progression rather than initiation of human melanoma. Cancer Res 63 (2003) 3883-3885
23. Rajagopalan H., Bardelli A., Lengauer C., Kinzler K.W., Vogelstein B., and Velculescu V.E. Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature 418 (2002) 934
24. Yuen S.T., Davies H., Chan T.L., Ho J.W., Bignell G.R., Cox C., Stephens P., Edkins S., Tsui W.W., Chan A.S., et al. Similarity of the phenotypic patterns associated with BRAF and KRAS mutations in colorectal neoplasia. Cancer Res 62 (2002) 6451-6455
25. Michaloglou C., Vredeveld L.C., Soengas M.S., Denoyelle C., Kuilman T., van der Horst C.M., Majoor D.M., Shay J.W., Mooi W.J., and Peeper D.S. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436 (2005) 720-724
26. Gray-Schopfer V.C., Cheong S.C., Chong H., Chow J., Moss T., Abdel-Malek Z.A., Marais R., Wynford-Thomas D., and Bennett D.C. Cellular senescence in naevi and immortalisation in melanoma: a role for p16?. Br J Cancer 95 (2006) 496-505
27. Slominski A., Tobin D.J., Shibahara S., and Wortsman J. Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev 84 (2004) 1155-1228
28. Curtin J.A., Fridlyand J., Kageshita T., Patel H.N., Busam K.J., Kutzner H., Cho K.H., Aiba S., Brocker E.B., LeBoit P.E., et al. Distinct sets of genetic alterations in melanoma. N Engl J Med 353 (2005) 2135-2147. Using array CGH, and BRAF and NRAS mutational profiling, the authors are able to distinguish among four groups of melanoma, differing in exposure to UV irradiation. 81% of melanomas on skin with no signs of chronic sun-induced damage had mutations in BRAF or NRAS.
29. Libra M., Malaponte G., Bevelacqua V., Siciliano R., Castrogiovanni P., Fulvi A., Micali G., Ligresti G., Mazzarino M.C., Stivala F., et al. Absence of BRAF gene mutation in non-melanoma skin tumors. Cell Cycle 5 (2006) 968-970
30. Gray-Schopfer V.C., da Rocha Dias S., and Marais R. The role of B-RAF in melanoma. Cancer Metastasis Rev 24 (2005) 165-183
31. Jaworski M., Buchmann A., Bauer P., Riess O., and Schwarz M. B-raf and Ha-ras mutations in chemically induced mouse liver tumors. Oncogene 24 (2005) 1290-1295
32. d'Ischia M., Napolitano A., and Prota G. Peroxidase as an alternative to tyrosinase in the oxidative polymerization of 5,6-dihydroxyindoles to melanin(s). Biochim Biophys Acta 1073 (1991) 423-430
33. Nappi A.J., and Vass E. Hydrogen peroxide generation associated with the oxidations of the eumelanin precursors 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid. Melanoma Res 6 (1996) 341-349
34. Ivanov V.N., Bhoumik A., and Ronai Z. Death receptors and melanoma resistance to apoptosis. Oncogene 22 (2003) 3152-3161
35. Gray-Schopfer VC, Karasarides M, Hayward R, Marais R: TNFα blocks apoptosis in melanoma cells when BRAF signalling is inhibited. Cancer Res in press.
36. Busca R., and Ballotti R. Cyclic AMP a key messenger in the regulation of skin pigmentation. Pigment Cell Res 13 (2000) 60-69
37. Rouzaud F., Kadekaro A.L., Abdel-Malek Z.A., and Hearing V.J. MC1R and the response of melanocytes to ultraviolet radiation. Mutat Res 571 (2005) 133-152
38. Landi M.T., Bauer J., Pfeiffer R.M., Elder D.E., Hulley B., Minghetti P., Calista D., Kanetsky P.A., Pinkel D., and Bastian B.C. MC1R germline variants confer risk for BRAF-mutant melanoma. Science 313 (2006) 521-522. The authors show that, in melanomas occurring on skin with few or no signs of chronic sun-induced damage, MC1R variants and BRAF mutations are strongly associated.
39. D'Orazio J.A., Nobuhisa T., Cui R., Arya M., Spry M., Wakamatsu K., Igras V., Kunisada T., Granter S.R., Nishimura E.K., et al. Topical drug rescue strategy and skin protection based on the role of Mc1r in UV-induced tanning. Nature 443 (2006) 340-344. Using mice possessing an inactivating MC1R mutation, the authors show that UV light fails to stimulate pigmentation in the absence of functional MC1R. This failure was rescued upon topical treatment with the cAMP agonist forskolin, emphasizing the role of MSH-MC1R signalling in the tanning response.
40. Valverde P., Healy E., Sikkink S., Haldane F., Thody A.J., Carothers A., Jackson I.J., and Rees J.L. The Asp84Glu variant of the melanocortin 1 receptor (MC1R) is associated with melanoma. Hum Mol Genet 5 (1996) 1663-1666
41. Mossner R., Anders N., Konig I.R., Kruger U., Schmidt D., Berking C., Ziegler A., Brockmoller J., Kaiser R., Volkenandt M., et al. Variations of the melanocortin-1 receptor and the glutathione-S transferase T1 and M1 genes in cutaneous malignant melanoma. Arch Dermatol Res (2006)
42. Debniak T., Scott R., Masojc B., Serrano-Fernandez P., Huzarski T., Byrski T., Debniak B., Gorski B., Cybulski C., Medrek K., et al. MC1R common variants, CDKN2A and their association with melanoma and breast cancer risk. Int J Cancer 119 (2006) 2597-2602
43. Kanetsky P.A., Rebbeck T.R., Hummer A.J., Panossian S., Armstrong B.K., Kricker A., Marrett L.D., Millikan R.C., Gruber S.B., Culver H.A., et al. Population-based study of natural variation in the melanocortin-1 receptor gene and melanoma. Cancer Res 66 (2006) 9330-9337
44. Han J., Kraft P., Colditz G.A., Wong J., and Hunter D.J. Melanocortin 1 receptor variants and skin cancer risk. Int J Cancer 119 (2006) 1976-1984
45. Stratigos A.J., Dimisianos G., Nikolaou V., Poulou M., Sypsa V., Stefanaki I., Papadopoulos O., Polydorou D., Plaka M., Christofidou E., et al. Melanocortin receptor-1 gene polymorphisms and the risk of cutaneous melanoma in a low-risk southern European population. J Invest Dermatol 126 (2006) 1842-1849
46. Fargnoli M.C., Altobelli E., Keller G., Chimenti S., Hofler H., and Peris K. Contribution of melanocortin-1 receptor gene variants to sporadic cutaneous melanoma risk in a population in central Italy: a case-control study. Melanoma Res 16 (2006) 175-182
47. Dumaz N., Hayward R., Martin J., Ogilvie L., Hedley D., Curtin J.A., Bastian B.C., Springer C., and Marais R. In melanoma, RAS mutations are accompanied by switching signaling from BRAF to CRAF and disrupted cyclic AMP signalling. Cancer Res 66 (2006) 9483-9491
48. Marais R., Light Y., Paterson H.F., Mason C.S., and Marshall C.J. Differential regulation of Raf-1, A-Raf, and B-Raf by oncogenic ras and tyrosine kinases. J Biol Chem 272 (1997) 4378-4383
49. Kumar R., Angelini S., Czene K., Sauroja I., Hahka-Kemppinen M., Pyrhonen S., and Hemminki K. BRAF mutations in metastatic melanoma: a possible association with clinical outcome. Clin Cancer Res 9 (2003) 3362-3368
50. Daniotti M., Oggionni M., Ranzani T., Vallacchi V., Campi V., Di Stasi D., Torre G.D., Perrone F., Luoni C., Suardi S., et al. BRAF alterations are associated with complex mutational profiles in malignant melanoma. Oncogene 23 (2004) 5968-5977
51. Haqq C., Nosrati M., Sudilovsky D., Crothers J., Khodabakhsh D., Pulliam B.L., Federman S., Miller III J.R., Allen R.E., Singer M.I., et al. The gene expression signatures of melanoma progression. Proc Natl Acad Sci USA 102 (2005) 6092-6097
52. Clark Jr. W.H., Elder D.E., Guerry Dt, Epstein M.N., Greene M.H., and Van Horn M. A study of tumor progression: the precursor lesions of superficial spreading and nodular melanoma. Hum Pathol 15 (1984) 1147-1165
53. Bittner M., Meltzer P., Chen Y., Jiang Y., Seftor E., Hendrix M., Radmacher M., Simon R., Yakhini Z., Ben-Dor A., et al. Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature 406 (2000) 536-540
54. Seftor E.A., Meltzer P.S., Kirschmann D.A., Pe'er J., Maniotis A.J., Trent J.M., Folberg R., and Hendrix M.J. Molecular determinants of human uveal melanoma invasion and metastasis. Clin Exp Metastasis 19 (2002) 233-246
55. de Wit N.J., Burtscher H.J., Weidle U.H., Ruiter D.J., and van Muijen G.N. Differentially expressed genes identified in human melanoma cell lines with different metastatic behaviour using high density oligonucleotide arrays. Melanoma Res 12 (2002) 57-69
56. Bloethner S., Chen B., Hemminki K., Muller-Berghaus J., Ugurel S., Schadendorf D., and Kumar R. Effect of common B-RAF and N-RAS mutations on global gene expression in melanoma cell lines. Carcinogenesis 26 (2005) 1224-1232
57. Pavey S., Johansson P., Packer L., Taylor J., Stark M., Pollock P.M., Walker G.J., Boyle G.M., Harper U., Cozzi S.J., et al. Microarray expression profiling in melanoma reveals a BRAF mutation signature. Oncogene 23 (2004) 4060-4067
58. Hoek K.S., Schlegel N.C., Brafford P., Sucker A., Ugurel S., Kumar R., Weber B.L., Nathanson K.L., Phillips D.J., Herlyn M., et al. Metastatic potential of melanomas defined by specific gene expression profiles with no BRAF signature. Pigment Cell Res 19 (2006) 290-302
59. Wan P.T., Garnett M.J., Roe S.M., Lee S., Niculescu-Duvaz D., Good V.M., Jones C.M., Marshall C.J., Springer C.J., Barford D., et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 116 (2004) 855-867
60. Garnett M.J., Rana S., Paterson H., Barford D., and Marais R. Wild-type and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization. Mol Cell 20 (2005) 963-969
61. Weber C.K., Slupsky J.R., Kalmes H.A., and Rapp U.R. Active Ras induces heterodimerization of cRaf and BRaf. Cancer Res 61 (2001) 3595-3598
62. Rushworth L.K., Hindley A.D., O'Neill E., and Kolch W. Regulation and role of Raf-1/B-Raf heterodimerization. Mol Cell Biol 26 (2006) 2262-2272
63. Chadee D.N., Xu D., Hung G., Andalibi A., Lim D.J., Luo Z., Gutmann D.H., and Kyriakis J.M. Mixed-lineage kinase 3 regulates B-Raf through maintenance of the B-Raf/Raf-1 complex and inhibition by the NF2 tumor suppressor protein. Proc Natl Acad Sci USA 103 (2006) 4463-4468
64. O'Neill E., Rushworth L., Baccarini M., and Kolch W. Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1. Science 306 (2004) 2267-2270
65. Chen J., Fujii K., Zhang L., Roberts T., and Fu H. Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEK-ERK independent mechanism. Proc Natl Acad Sci USA 98 (2001) 7783-7788
66. Ehrenreiter K., Piazzolla D., Velamoor V., Sobczak I., Small J.V., Takeda J., Leung T., and Baccarini M. Raf-1 regulates Rho signaling and cell migration. J Cell Biol 168 (2005) 955-964
67. Rapp U.R., Rennefahrt U., and Troppmair J. Bcl-2 proteins: master switches at the intersection of death signaling and the survival control by Raf kinases. Biochim Biophys Acta 1644 (2004) 149-158
68. Cox A.D., and Der C.J. The dark side of Ras: regulation of apoptosis. Oncogene 22 (2003) 8999-9006
69. Schubbert S., Zenker M., Rowe S.L., Boll S., Klein C., Bollag G., van der Burgt I., Musante L., Kalscheuer V., Wehner L.E., et al. Germline KRAS mutations cause Noonan syndrome. Nat Genet 38 (2006) 331-336
70. Aoki Y., Niihori T., Kawame H., Kurosawa K., Ohashi H., Tanaka Y., Filocamo M., Kato K., Suzuki Y., Kure S., et al. Germline mutations in HRAS proto-oncogene cause Costello syndrome. Nat Genet 37 (2005) 1038-1040
71. Niihori T., Aoki Y., Narumi Y., Neri G., Cave H., Verloes A., Okamoto N., Hennekam R.C., Gillessen-Kaesbach G., Wieczorek D., et al. Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Nat Genet 38 (2006) 294-296
72. Rodriguez-Viciana P., Tetsu O., Tidyman W.E., Estep A.L., Conger B.A., Cruz M.S., McCormick F., and Rauen K.A. Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome. Science 311 (2006) 1287-1290
73. Duesbery N., and Vande Woude G. BRAF and MEK mutations make a late entrance. Sci STKE 2006 (2006) pe15
74. Mercer K., Giblett S., Green S., Lloyd D., DaRocha Dias S., Plumb M., Marais R., and Pritchard C. Expression of endogenous oncogenic V600EB-raf induces proliferation and developmental defects in mice and transformation of primary fibroblasts. Cancer Res 65 (2005) 11493-11500