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Linked References

1. National Cancer Institute SEER Stat Fact Sheets, “Melanoma of the skin,” 2010, http://seer.cancer.gov/statfacts/html/melan.html. View at Google Scholar
2. National Cancer Institute Skin Cancer, 2010, http://www.cancer.gov/cancertopics/types/skin.
3. N. Ibrahim and F. G. Haluska, “Molecular pathogenesis of cutaneous melanocytic neoplasms,” Annual Review of Pathology, vol. 4, pp. 551–579, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
4. A. E. Chang, L. H. Karnell, and H. R. Menck, “The national cancer data base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade: the American College of Surgeons Commission on Cancer and the American Cancer Society,” Cancer, vol. 83, no. 8, pp. 1664–1678, 1998. View at Google Scholar
5. N. V. Laver, M. E. McLaughlin, and J. S. Duker, “Ocular melanoma,” Archives of Pathology and Laboratory Medicine, vol. 134, no. 12, pp. 1778–1784, 2010. View at Google Scholar · View at Scopus
6. B. Damato, “Does ocular treatment of uveal melanoma influence survival,” British Journal of Cancer, vol. 103, no. 3, pp. 285–290, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
7. I. Yeh and B. C. Bastian, “Genome-wide associations studies for melanoma and nevi,” Pigment Cell and Melanoma Research, vol. 22, no. 5, pp. 527–528, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
8. K. B. Calder and M. B. Morgan, “Carcinogenic pathway of malignant melanoma,” in Mechanisms of Oncogenesis: An Update on Tumorigenesis, D. Coppola, Ed., pp. 149–157, Springer, 2010. View at Google Scholar
9. K. D. Meyle and P. Guldberg, “Genetic risk factors for melanoma,” Human Genetics, vol. 126, no. 4, pp. 499–510, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
10. A. A. Nelson and H. Tsao, “Melanoma and genetics,” Clinics in Dermatology, vol. 27, no. 1, pp. 46–52, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
11. G. Palmieri, M. Capone, M. L. Ascierto et al., “Main roads to melanoma,” Journal of Translational Medicine, vol. 7, Article ID 86, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
12. A. Sekulic, P. Haluska, A. J. Miller et al., “Malignant melanoma in the 21st century: the emerging molecular landscape,” Mayo Clinic Proceedings, vol. 83, no. 7, pp. 825–846, 2008. View at Publisher · View at Google Scholar · View at Scopus
13. L. Chin, “The genetics of malignant melanoma: lessons from mouse and man,” Nature Reviews Cancer, vol. 3, no. 8, pp. 559–570, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
14. K. S. Smalley, “Understanding melanoma signaling networks as the basis for molecular targeted therapy,” Journal of Investigative Dermatology, vol. 130, no. 1, pp. 28–37, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
15. Y. Kong, S. M. Kumar, and X. Xu, “Molecular pathogenesis of sporadic melanoma and melanoma-initiating cells,” Archives of Pathology and Laboratory Medicine, vol. 134, no. 12, pp. 1740–1749, 2010. View at Google Scholar · View at Scopus
16. Y. Yarden, W. J. Kuang, T. Yang-Feng et al., “Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand,” EMBO Journal, vol. 6, no. 11, pp. 3341–3351, 1987. View at Google Scholar · View at Scopus
17. S. E. Woodman and M. A. Davies, “Targeting KIT in melanoma: a paradigm of molecular medicine and targeted therapeutics,” Biochemical Pharmacology, vol. 80, no. 5, pp. 568–574, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
18. K. T. Flaherty, F. S. Hodi, and B. C. Bastian, “Mutation-driven drug development in melanoma,” Current Opinion in Oncology, vol. 22, no. 3, pp. 178–183, 2010. View at Publisher · View at Google Scholar · View at Scopus
19. C. R. Antonescu, K. J. Busam, T. D. Francone et al., “L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition,” International Journal of Cancer, vol. 121, no. 2, pp. 257–264, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
20. A. Ashida, M. Takata, H. Murata, K. Kido, and T. Saida, “Pathological activation of KIT In metastatic tumors of acral and mucosal melanomas,” International Journal of Cancer, vol. 124, no. 4, pp. 863–868, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
21. C. Beadling, E. Jacobson-Dunlop, F. S. Hodi et al., “KIT gene mutations and copy number in melanoma subtypes,” Clinical Cancer Research, vol. 14, no. 21, pp. 6821–6828, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
22. J. A. Curtin, K. Busam, D. Pinkel, and B. C. Bastian, “Somatic activation of KIT in distinct subtypes of melanoma,” Journal of Clinical Oncology, vol. 24, no. 26, pp. 4340–4346, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
23. R. S. Rivera, H. Nagatsuka, M. Gunduz et al., “C-kit protein expression correlated with activating mutations in KIT gene in oral mucosal melanoma,” Virchows Archiv, vol. 452, no. 1, pp. 27–32, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
24. K. S. Smalley, V. K. Sondak, and J. S. Weber, “C-KIT signaling as the driving oncogenic event in sub-groups of melanomas,” Histology and Histopathology, vol. 24, no. 5, pp. 643–650, 2009. View at Google Scholar · View at Scopus
25. J. Lennartsson, P. Blume-Jensen, M. Hermanson, E. Pontén, M. Carlberg, and L. Rönnstrand, “Phosphorylation of Shc by Src family kinases is necessary for stem cell factor receptor/c-kit mediated activation of the Ras/MAP kinase pathway and c-fos induction,” Oncogene, vol. 18, no. 40, pp. 5546–5553, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
26. C. D. Mol, D. R. Dougan, T. R. Schneider et al., “Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase,” Journal of Biological Chemistry, vol. 279, no. 30, pp. 31655–31663, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
27. A. Platz, S. Egyhazi, U. Ringborg, and J. Hansson, “Human cutaneous melanoma; a review of NRAS and BRAF mutation frequencies in relation to histogenetic subclass and body site,” Molecular Oncology, vol. 1, no. 4, pp. 395–405, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
28. J. Ackermann, M. Frutschi, K. Kaloulis, T. McKee, A. Trumpp, and F. Beermann, “Metastasizing melanoma formation caused by expression of activated ${\text{N-Ras}}^{\text{Q61K}}$ on an INK4a-deficient background,” Cancer Research, vol. 65, no. 10, pp. 4005–4011, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
29. L. Chin, A. Tam, J. Pomerantz et al., “Essential role for oncogenic ras in tumour maintenance,” Nature, vol. 400, no. 6743, pp. 468–472, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
30. P. M. Pollock, U. L. Harper, K. S. Hansen et al., “High frequency of BRAF mutations in nevi,” Nature Genetics, vol. 33, no. 1, pp. 19–20, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
31. I. Puzanov and K. T. Flaherty, “Targeted molecular therapy in melanoma,” Seminars in Cutaneous Medicine and Surgery, vol. 29, no. 3, pp. 196–201, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
32. P. T. C. Wan, M. J. Garnett, S. M. Roe et al., “Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF,” Cell, vol. 116, no. 6, pp. 855–867, 2004. View at Publisher · View at Google Scholar · View at Scopus
33. V. K. Goel, A. J. F. Lazar, C. L. Warneke, M. S. Redston, and F. G. Haluska, “Examination of mutations in BRAF, NRAS, and PTEN in primary cutaneous melanoma,” Journal of Investigative Dermatology, vol. 126, no. 1, pp. 154–160, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
34. A. Mirmohammadsadegh, A. Marini, S. Nambiar et al., “Epigenetic silencing of the PTEN gene in melanoma,” Cancer Research, vol. 66, no. 13, pp. 6546–6552, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
35. H. Tsao, V. K. Goel, H. Wu, G. Yang, and F. G. Haluska, “Genetic interaction between NRAS and BRAF mutations and PTEN/MMAC1 inactivation in melanoma,” Journal of Investigative Dermatology, vol. 122, no. 2, pp. 337–341, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
36. A. Zembowicz, R. V. Mandal, and P. Choopong, “Melanocytic lesions of the conjunctiva,” Archives of Pathology and Laboratory Medicine, vol. 134, no. 12, pp. 1785–1792, 2010. View at Google Scholar · View at Scopus
37. “Intraocular (Eye) melanoma treatment,” 2007, http://www.cancer.gov/cancertopics/pdq/treatment/intraocularmelanoma/HealthProfessional.
38. A. M. Goldstein, S. N. Stacey, J. H. Olafsson et al., “CDKN2A mutations and melanoma risk in the Icelandic population,” Journal of Medical Genetics, vol. 45, no. 5, pp. 284–289, 2008. View at Google Scholar · View at Scopus
39. F. Cruz, B. P. Rubin, D. Wilson et al., “Absence of BRAF and NRAS mutations in uveal melanoma,” Cancer Research, vol. 63, no. 18, pp. 5761–5766, 2003. View at Google Scholar · View at Scopus
40. D. Rimoldi, S. Salvi, D. Liénard et al., “Lack of BRAF mutations in uveal melanoma,” Cancer Research, vol. 63, no. 18, pp. 5712–5715, 2003. View at Google Scholar · View at Scopus
41. W. Zuidervaart, F. Van Nieuwpoort, M. Stark et al., “Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS,” British Journal of Cancer, vol. 92, no. 11, pp. 2032–2038, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
42. M. D. Onken, L. A. Worley, M. D. Long et al., “Oncogenic mutations in GNAQ occur early in uveal melanoma,” Investigative Ophthalmology and Visual Science, vol. 49, no. 12, pp. 5230–5234, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
43. M. Patel, E. Smyth, P. B. Chapman, et al., “Therapeutic implications of the emerging molecular biology of uveal melanoma,” Clinical Cancer Research, vol. 17, no. 8, pp. 2087–2100, 2011. View at Publisher · View at Google Scholar · View at PubMed
44. C. D. Van Raamsdonk, V. Bezrookove, G. Green et al., “Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi,” Nature, vol. 457, no. 7229, pp. 599–602, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
45. “Phase II trial of temozolomide versus AZD6244 in patients with metastatic uveal melanoma,” 2011, http://www.mskcc.org/mskcc/html/2270.cfm?IRBNO=10-053.
46. H. Davies, G. R. Bignell, C. Cox et al., “Mutations of the BRAF gene in human cancer,” Nature, vol. 417, no. 6892, pp. 949–954, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
47. D. J. Nancarrow, G. J. Mann, E. A. Holland et al., “Confirmation of chromosome 9p linkage in familial melanoma,” American Journal of Human Genetics, vol. 53, no. 4, pp. 936–942, 1993. View at Google Scholar · View at Scopus
48. R. A. Padua, N. C. Barrass, and G. A. Currie, “Activation of N-ras in a human melanoma cell line,” Molecular and Cellular Biology, vol. 5, no. 3, pp. 582–585, 1985. View at Google Scholar · View at Scopus
49. P. A. Steck, M. A. Pershouse, S. A. Jasser et al., “Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers,” Nature Genetics, vol. 15, no. 4, pp. 356–362, 1997. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
50. L. Zuo, J. Weger, Q. Yang et al., “Germline mutations in the p16(INK4a) binding domain of CDK4 in familial melanoma,” Nature Genetics, vol. 12, no. 1, pp. 97–99, 1996. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
51. U. Benbow, G. B. Tower, C. A. Wyatt, G. Buttice, and C. E. Brinckerhoff, “High levels of MMP-1 expression in the absence of the 2G single nucleotide polymorphism is mediated by p38 and ERK1/2 mitogen-activated protein kinases in VMM5 melanoma cells,” Journal of Cellular Biochemistry, vol. 86, no. 2, pp. 307–319, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
52. R. A. Cartlidge, G. R. Thomas, S. Cagnol et al., “Oncogenic ${\text{BRAF}}^{\text{V600E}}$ inhibits BIM expression to promote melanoma cell survival,” Pigment Cell and Melanoma Research, vol. 21, no. 5, pp. 534–544, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
53. K. M. Eisenmann, M. W. VanBrocklin, N. A. Staffend, S. M. Kitchen, and H. M. Koo, “Mitogen-activated protein kinase pathway-dependent tumor-specific survival signaling in melanoma cells through inactivation of the proapoptotic protein bad,” Cancer Research, vol. 63, no. 23, pp. 8330–8337, 2003. View at Google Scholar · View at Scopus
54. J. T. Huntington, J. M. Shields, C. J. Der et al., “Overexpression of collagenase 1 (MMP-1) is mediated by the ERK pathway in invasive melanoma cells: role of BRAF mutation and fibroblast growth factor signaling,” Journal of Biological Chemistry, vol. 279, no. 32, pp. 33168–33176, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
55. M. Kono, I. S. Dunn, P. J. Durda et al., “Role of the mitogen-activated protein kinase signaling pathway in the regulation of human melanocytic antigen expression,” Molecular Cancer Research, vol. 4, no. 10, pp. 779–792, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
56. S. M. Kumar, H. Yu, R. Edwards et al., “Mutant V600E BRAF increases hypoxia inducible factor-1α expression in melanoma,” Cancer Research, vol. 67, no. 7, pp. 3177–3184, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
57. A. Sharma, M. A. Tran, S. Liang et al., “Targeting mitogen-activated protein kinase/extracellular signal-regulated kinase kinase in the mutant (V600E) B-Raf signaling cascade effectively inhibits melanoma lung metastases,” Cancer Research, vol. 66, no. 16, pp. 8200–8209, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
58. A. Sharma, N. R. Trivedi, M. A. Zimmerman, D. A. Tuveson, C. D. Smith, and G. P. Robertson, “Mutant ${}^{\text{V599E}}\text{B}\text{-Raf}$ regulates growth and vascular development of malignant melanoma tumors,” Cancer Research, vol. 65, no. 6, pp. 2412–2421, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
59. M. S. Soengas and S. W. Lowe, “Apoptosis and melanoma chemoresistance,” Oncogene, vol. 22, no. 20, pp. 3138–3151, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
60. H. Sumimoto, F. Imabayashi, T. Iwata, and Y. Kawakami, “The BRAF-MAPK signaling pathway is essential for cancer-immune evasion in human melanoma cells,” Journal of Experimental Medicine, vol. 203, no. 7, pp. 1651–1656, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
61. D. Woods, H. Cherwinski, E. Venetsanakos et al., “Induction of β3-integrin gene expression by sustained activation of the Ras-regulated Raf-MEK-extracellular signal-regulated kinase signaling pathway,” Molecular and Cellular Biology, vol. 21, no. 9, pp. 3192–3205, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
62. X. D. Zhang, J. M. Borrow, X. Y. Zhang, T. Nguyen, and P. Hersey, “Activation of ERK1/2 protects melanoma cells from TRAIL-induced apoptosis by inhibiting Smac/DIABLO release from mitochondria,” Oncogene, vol. 22, no. 19, pp. 2869–2881, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
63. J. Newton-Bishop and N. Gruis, “Melanoma susceptibility genes,” Melanoma Research, vol. 20, no. 3, pp. 161–162, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
64. D. T. Bishop, F. Demenais, M. M. Iles et al., “Genome-wide association study identifies three loci associated with melanoma risk,” Nature Genetics, vol. 41, no. 8, pp. 920–925, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
65. M. Falchi, V. Bataille, N. K. Hayward et al., “Genome-wide association study identifies variants at 9p21 and 22q13 associated with development of cutaneous nevi,” Nature Genetics, vol. 41, no. 8, pp. 915–919, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
66. I. Puzanov, K. L. Nathanson, P. B. Chapman, et al., “PLX4032, a highly selective ${}^{\text{V600E}}\text{B}\text{RAF}$ kinase inhibitor: clinical correlation of activity with pharmacokinetic and pharmacodynamic parameters in a phase I trial,” Journal of Clinical Oncology, vol. 27, no. 15s, p. 9021, 2009. View at Google Scholar
67. F. S. Hodi, P. Friedlander, C. L. Corless et al., “Major response to imatinib mesylate in KIT-mutated melanoma,” Journal of Clinical Oncology, vol. 26, no. 12, pp. 2046–2051, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus