Genetics and genomics of melanoma

Expert Review of Dermatology

Volumn 4, Issue 2, 2009, Pages 131-143

  Ghosh, Papia ^a   Chin, Lynda ^a  

^a DANA FARBER CANCER INSTITUTE   (United States)

Author keywords

Array comparative genomic hybridization; BRAF; CDKN2A; Genomics; MAPK; Metastasis; N RAS; P13K; Receptor tyrosine kinase

Indexed keywords

B RAF KINASE; CYCLIN DEPENDENT KINASE INHIBITOR 2A; EPIDERMAL GROWTH FACTOR RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; RAS PROTEIN; SCATTER FACTOR RECEPTOR; STEM CELL FACTOR RECEPTOR; TYROSINE KINASE RECEPTOR;

CANCER GENETICS; CANCER GROWTH; CELL PROLIFERATION; CHROMATIN IMMUNOPRECIPITATION; CUTANEOUS MELANOMA; DNA HYBRIDIZATION; DNA METHYLATION; DNA SEQUENCE; GENE EXPRESSION PROFILING; GENETIC HETEROGENEITY; GENOME ANALYSIS; HUMAN; IMMUNOHISTOCHEMISTRY; MALIGNANT LENTIGO; MELANOCYTE; MELANOMA; NONHUMAN; POINT MUTATION; PRIORITY JOURNAL; RADIATION EXPOSURE; REVIEW; SIGNAL TRANSDUCTION; SKIN CARCINOGENESIS; SUN EXPOSURE; TUMOR VOLUME; ULTRAVIOLET RADIATION;

EID: 70049104593     PISSN: 17469872     EISSN: None     Source Type: Journal    
DOI: 10.1586/edm.09.2     Document Type: Review

References (147)

1. Gray-Schopfer V, Wellbrock C, Marais R. Melanoma biology and new targeted therapy. Nature 445(7130), 851-857 (2007).
2. National Cancer Institute. SEER Cancer Statistics Review, 1975-2005. Ries LAG, Melbert D, Krapcho M, Stinchcomb DG et al. (Eds). National Cancer Institute. Bethesda, MD, USA (2008).
3. Rigel DS. Cutaneous ultraviolet exposure and its relationship to the development of skin cancer. J. Am. Acad. Dermatol. 58(5 Suppl. 2), S129-S132 (2008).
4. Chin L. The genetics of malignant melanoma: lessons from mouse and man. Nat. Rev. Cancer 3(8), 559-570 (2003).
5. Swetter SM, Boldrick JC, Jung SY, Egbert BM, Harvell JD. Increasing incidence of lentigo maligna melanoma subtypes: northern California and national trends 1990-2000. J. Invest. Dermatol. 125(4), 685-691 (2005).
6. Forman SB, Ferringer TC, Peckham SJ et al. Is superficial spreading melanoma still the most common form of malignant melanoma? J. Am. Acad. Dermatol. 58(6), 1013-1020 (2008).
7. Balch CM, Soong SJ, Gershenwald JE et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J. Clin. Oncol. 19, 3622-3634 (2001).
8. Gimotty PA, Van Belle P, Elder DE et al. Biologic and prognostic significance of dermal Ki67 expression, mitoses, and tumorigenicity in thin invasive cutaneous melanoma. J. Clin. Oncol. 23(31), 8048-8056 (2005).
9. Gilchrest BA, Eller MS, Geller AC, Yaar M. The pathogenesis of melanoma induced by ultraviolet radiation. N. Engl. J. Med. 340(17), 1341-1348 (1999).
10. Gandini S, Sera F, Cattaruzza MS et al. Meta-analysis of risk factors for cutaneous melanoma: I. Common and atypical naevi. Eur. J. Cancer 41(1), 28-44 (2005).
11. Ford D, Bliss JM, Swerdlow AJ et al. The International Melanoma Analysis Group (IMAGE). Risk of cutaneous melanoma associated with a family history of the disease. Int. J. Cancer 62(4), 377-381 (1995).
12. Gandini S, Sera F, Cattaruzza MS et al. Meta-analysis of risk factors for cutaneous melanoma: III. Family history, actinic damage and phenotypic factors. Eur. J. Cancer 41(14), 2040-2059 (2005).
13. Hussussian CJ, Struewing JP, Goldstein AM et al. Germline p16 mutations in familial melanoma. Nat. Genet. 8(1), 15-21 (1994).
14. Kamb A, Shattuck-Eidens D, Eeles R et al. Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus. Nat. Genet. 8(1), 23-26 (1994).
15. Chin L, Garraway LA, Fisher DE. Malignant melanoma: genetics and therapeutics in the genomic era. Genes Dev. 20(16), 2149-2182 (2006).
16. Aitken J, Welch J, Duffy D et al. CDKN2A variants in a population-based sample of Queensland families with melanoma. J. Natl Cancer Inst. 91(5), 446-452 (1999).
17. Tsao H, Zhang X, Kwitkiwski K et al. Low prevalence of germline CDKN2A and CDK4 mutations in patients with early-onset melanoma. Arch. Dermatol. 136(9), 1118-1122 (2000).
18. Wolfel T, Hauer M, Schneider J et al. A p16INK4α-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science 269(5228), 1281-1284 (1995).
19. Zuo L, Weger J, Yang Q et al. Germline mutations in the p 16INK4α binding domain of CDK4 in familial melanoma. Nat. Genet. 12(1), 97-99 (1996).
20. Molven A, Grimstvedt MB, Steine SJ et al. A large Norwegian family with inherited malignant melanoma, multiple atypical nevi, and CDK4 mutation. Genes Chromosomes Cancer 44(1), 10-18 (2005).
21. Draper GJ, Sanders BM, Kingston JE. Second primary neoplasms in patients with retinoblastoma. Br. J. Cancer 53(5), 661-671 (1986).
22. Fletcher O, Easton D, Anderson K et al. Lifetime risks of common cancers among retinoblastoma survivors. J. Natl Cancer Inst. 96(5), 357-363 (2004).
23. Albino AP, Vidal MJ, McNutt NS et al. Mutation and expression of the p53 gene in human malignant melanoma. Melanoma Res. 4(1), 35-45 (1994).
24. Castresana JS, Rubio MP, Vazquez JJ et al. Lack of allelic deletion and point mutation as mechanisms of p53 activation in human malignant melanoma. Int. J. Cancer 55(4), 562-565 (1993).
25. Lubbe J, Reichel M, Burg G, Kleihues P. Absence of p53 gene mutations in cutaneous melanoma. J. Invest. Dermatol. 102(5), 819-821 (1994).
26. Bardeesy N, Bastian BC, Hezel A et al. Dual inactivation of RB and p53 pathways in RAS-induced melanomas. Mol. Cell. Biol. 21(6), 2144-2153 (2001).
27. Chin L, Pomerantz J, Polsky D et al. Cooperative effects of INK4a and ras in melanoma susceptibility in vivo. Genes Dev. 11(21), 2822-2834 (1997).
28. Bastian BC, LeBoit PE, Hamm H, Brocker EB, Pinkel D. Chromosomal gains and losses in primary cutaneous melanomas detected by comparative genomic hybridization. Cancer Res. 58(10), 2170-2175 (1998).
29. Koprowski H, Herlyn M, Balaban G et al. Expression of the receptor for epidermal growth factor correlates with increased dosage of chromosome 7 in malignant melanoma. Somat. Cell Mol. Genet. 11(3), 297-302 (1985).
30. Udart M, Utikal J, Krahn GM, Peter RU. Chromosome 7 aneusomy. A marker for metastatic melanoma? Expression of the epidermal growth factor receptor gene and chromosome 7 aneusomy in nevi, primary malignant melanomas and metastases. Neoplasia 3(3), 245-254 (2001).
31. Bardeesy N, Kim M, Xu J et al. Role of epidermal growth factor receptor signaling in RAS-driven melanoma. Mol. Cell. Biol. 25(10), 4176-4188 (2005).
32. Dlugosz AA, Hansen L, Cheng C et al. Targeted disruption of the epidermal growth factor receptor impairs growth of squamous papillomas expressing the v-ras(Ha) oncogene but does not block in vitro keratinocyte responses to oncogenic ras. Cancer Res. 57(15), 3180-3188 (1997).
33. Gangarosa LM, Sizemore N, Graves-Deal R et al. A raf-independent epidermal growth factor receptor autocrine loop is necessary for Ras transformation of rat intestinal epithelial cells. J. Biol. Chem. 272(30), 18926-18931 (1997).
34. Sibilia M, Fleischmann A, Behrens A et al. The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development. Cell 102(2), 211-220 (2000).
35. Bottaro DP, Rubin JS, Faletto DL. Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 251, 802-804 (1991).
36. Wiltshire RN, Duray P, Bittner ML et al. Direct visualization of the clonal progression of primary cutaneous melanoma: application of tissue microdissection and comparative genomic hybridization. Cancer Res. 55, 3954-3957 (1995).
37. Natali PG, Nicotra MR, Di Renzo MF et al. Expression of the c-Met/ HGF receptor in human melanocytic neoplasms: demonstration of the relationship to malignant melanoma tumour progression. Br. J. Cancer 68(4), 746-750 (1993).
38. Vande Woude GF, Jeffers M, Cortner J et al. Met-HGF/SF: tumorigenesis, invasion and metastasis. Ciba Found. Symp. 212, 119-130 (1997).
39. Rusciano D, Lorenzoni P, Burger MM. Expression of constitutively activated hepatocyte growth factor/scatter factor receptor (c-met) in B16 melanoma cells selected for enhanced liver colonization. Oncogene 11(10), 1979-1987 (1995).
40. Otsuka T, Takayama H, Sharp R et al. c-Met autocrine activation induces development of malignant melanoma and acquisition of the metastatic phenotype. Cancer Res. 58(22), 5157-5167 (1998).
41. Noonan FP, Recio JA, Takayama H et al. Neonatal sunburn and melanoma in mice. Nature 413(6853), 271-272 (2001).
42. Recio JA, Noonan FP, Takayama H et al. Ink4a/arf deficiency promotes ultraviolet radiation-induced melanomagenesis. Cancer Res. 62(22), 6724-6730 (2002).
43. McGill GG, Haq R, Nishimura EK, Fisher DE. c-Met expression is regulated by Mitf in the melanocyte lineage. J. Biol. Chem. 281(15), 10365-10373 (2006).
44. Garraway LA, Widlund HR, Rubin MA et al. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature 436(7047), 117-122 (2005).
45. Montone KT, van Belle P, Elenitsas R, Elder DE. Proto-oncogene c-kit expression in malignant melanoma: protein loss with tumor progression. Mod. Pathol. 10(9), 939-944 (1997).
46. Shen SS, Zhang PS, Eton O, Prieto VG. Analysis of protein tyrosine kinase expression in melanocytic lesions by tissue array. J. Cutan. Pathol. 30(9), 539-547 (2003).
47. Isabel Zhu Y, Fitzpatrick JE. Expression of c-kit (CD117) in Spitz nevus and malignant melanoma. J. Cutan. Pathol. 33(1), 33-37 (2006).
48. Huang S, Luca M, Gutman M et al. Enforced c-KIT expression renders highly metastatic human melanoma cells susceptible to stem cell factor-induced apoptosis and inhibits their tumorigenic and metastatic potential. Oncogene 13, 2339-2347 (1996).
49. Yoshida H, Kunisada T, Kusakabe M, Nishikawa S, Nishikawa SI. Distinct stages of melanocyte differentiation revealed by anlaysis of nonuniform pigmentation patterns. Development 122(4), 1207-1214 (1996).
50. Grichnik JM, Burch JA, Burchette J, Shea CR. The SCF/KIT pathway plays a critical role in the control of normal human melanocyte homeostasis. J. Invest. Dermatol. 111(2), 233-238 (1998).
51. Sviderskaya EV, Wakeling WF, Bennett DC. A cloned, immortal line of murine melanoblasts inducible to differentiate to melanocytes. Development 121(5), 1547-1557 (1995).
52. Willmore-Payne C, Holden JA, Tripp S, Lay?eld LJ. Human malignant melanoma: detection of BRAF- and c-kit-activating mutations by high-resolution amplicon melting analysis. Hum. Pathol. 36(5), 486-493 (2005).
53. Willmore-Payne C, Holden JA, Hirschowitz S, Layfield LJ. BRAF and c-kit gene copy number in mutation-positive malignant melanoma. Hum. Pathol. 37(5), 520-527 (2006).
54. Nakahara M, Isozaki K, Hirota S et al. A novel gain-of-function mutation of c-kit gene in gastrointestinal stromal tumors. Gastroenterology 115(5), 1090-1095 (1998).
55. Fukuda R, Hamamoto N, Uchida Y et al. Gastrointestinal stromal tumor with a novel mutation of KIT proto-oncogene. Intern. Med. 40(4), 301-303 (2001).
56. Curtin JA, Busam K, Pinkel D, Bastian BC. Somatic activation of KIT in distinct subtypes of melanoma. J. Clin. Oncol. 24(26), 4340-4346 (2006).
57. Beadling C, Jacobson-Dunlop E, Hodi FS et al. KIT gene mutations and copy number in melanoma subtypes. Clin. Cancer Res. 14(21), 6821-6828 (2008).
58. van Oosterom AT, Judson IR, Verweij J et al. Update of Phase I study of imatinib (STI571) in advanced soft tissue sarcomas and gastrointestinal stromal tumors: a report of the EORTC Soft Tissue and Bone Sarcoma Group. Eur. J. Cancer 38(Suppl. 5), S83-S87 (2002).
59. van Oosterom AT, Judson I, Verweij J et al. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a Phase I study. Lancet 358(9291), 1421-1423 (2001).
60. Verweij J, Casali PG, Zalcberg J et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 364(9440), 1127-1134 (2004).
61. Demetri GD, von Mehren M, Blanke CD et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N. Engl. J. Med. 347(7), 472-480 (2002).
62. Hodi FS, Friedlander P, Corless CL et al. Major response to imatinib mesylate in KIT-mutated melanoma. J. Clin. Oncol. 26(12), 2046-2051 (2008).
63. Lutzky J, Bauer J, Bastian BC. Dose-dependent, complete response to imatinib of a metastatic mucosal melanoma with a K642E KIT mutation. Pigment Cell Melanoma Res. 21(4), 492-493 (2008).
64. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 100(1), 57-70 (2000).
65. Jafari M, Papp T, Kirchner S et al. Analysis of ras mutations in human melanocytic lesions: activation of the ras gene seems to be associated with the nodular type of human malignant melanoma. J. Cancer Res. Clin. Oncol. 121(1), 23-30 (1995).
66. van Elsas A, Zerp SF, van der Flier S et al. Relevance of ultraviolet-induced N-ras oncogene point mutations in development of primary human cutaneous melanoma. Am. J. Pathol. 149(3), 883-893 (1996).
67. Papp T, Pemsel H, Zimmermann R et al. Mutational analysis of the N-ras, p53, p16INK4a, CDK4, and MC1R genes in human congenital melanocytic naevi. J. Med. Genet. 36, 610-614 (1999).
68. Albino AP, Nanus DM, Mentle IR et al. Analysis of ras oncogenes in malignant melanoma and precursor lesions: correlation of point mutations with differentiation phenotype. Oncogene 4, 1363-1374 (1989).
69. Bastian BC, LeBoit PE, Pinkel D. Mutations and copy number increase of HRAS in Spitz nevi with distinctive histopathological features. Am. J. Pathol., 157, 967-972 (2000).
70. Barnhill RL. The Spitzoid lesion: rethinking Spitz tumors, atypical variants, 'Spitzoid melanoma' and risk assessment. Mod. Pathol. 19(Suppl. 2), S21-S33 (2006).
71. Smith KJ, Barrett TL, Skelton HG, 3rd, Lupton GP, Graham JH. Spindle cell and epithelioid cell nevi with atypia and metastasis (malignant Spitz nevus). Am. J. Surg. Pathol. 13(11), 931-939 (1989).
72. Sharpless NE, Kannan K, Xu J, Bosenberg MW, Chin L. Both products of the mouse Ink4a/Arf locus suppress melanoma formation in vivo. Oncogene 22(32), 5055-5059 (2003).
73. Ackermann J, Frutschi M, Kaloulis K et al. Metastasizing melanoma formation caused by expression of activated N-RasQ61K on an INK4a-deficient background. Cancer Res. 65(10), 4005-4011 (2005).
74. Davies H, Bignell GR, Cox C et al. Mutations of the BRAF gene in human cancer. Nature 417(6892), 949-954 (2002).
75. Lang J, Boxer M, MacKie R. Absence of exon 15 BRAF germline mutations in familial melanoma. Hum. Mutat. 21(3), 327-330 (2003).
76. Casula M, Colombino M, Satta MP et al. 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(2), 286-292 (2004).
77. Laud K, Kannengiesser C, Avril MF et al. BRAF as a melanoma susceptibility candidate gene? Cancer Res. 63(12), 3061-3065 (2003).
78. Liu J, Suresh Kumar KG, Yu D et al. Oncogenic BRAF regulates β-Trcp expression and NF-κB activity in human melanoma cells. Oncogene 26(13), 1954-1958 (2007).
79. Bhatt KV, Hu R, Spofford LS, Aplin AE. Mutant B-RAF signaling and cyclin D1 regulate Cks1/S-phase kinase-associated protein 2-mediated degradation of p27Kip1 in human melanoma cells. Oncogene 26(7), 1056-1066 (2007).
80. Garnett MJ, Marais R. Guilty as charged: B-RAF is a human oncogene. Cancer Cell 6(4), 313-319 (2004).
81. Maldonado JL, Fridlyand J, Patel H et al. Determinants of BRAF mutations in primary melanomas. J. Natl Cancer Inst. 95(24), 1878-1890 (2003).
82. Edwards RH, Ward MR, Wu H et al. Absence of BRAF mutations in UV-protected mucosal melanomas. J. Med. Genet. 41(4), 270-272 (2004).
83. Curtin JA, Fridlyand J, Kageshita T et al. Distinct sets of genetic alterations in melanoma. N. Engl. J. Med. 353(20), 2135-2147 (2005).
84. Landi MT, Bauer J, Pfeiffer RM et al. MC1R germline variants confer risk for BRAF-mutant melanoma. Science 313(5786), 521-522 (2006).
85. Kennedy C, ter Huurne J, Berkhout M et al. 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(2), 294-300 (2001).
86. Duffy DL, Box NF, Chen W et al. Interactive effects of MC1R and OCA2 on melanoma risk phenotypes. Hum. Mol. Genet. 13(4), 447-461 (2004).
87. Raimondi S, Sera F, Gandini S et al. MC1R variants, melanoma and red hair color phenotype: a meta-analysis. Int. J. Cancer 122(12), 2753-2760 (2008).
88. Pollock PM, Harper UL, Hansen KS et al. High frequency of BRAF mutations in nevi. Nat. Genet. 33(1), 19-20 (2003).
89. Kumar R, Angelini S, Snellman E, Hemminki K. BRAF mutations are common somatic events in melanocytic nevi. J. Invest. Dermatol. 122(2), 342-348 (2004).
90. Saldanha G, Purnell D, Fletcher A et al. High BRAF mutation frequency does not characterize all melanocytic tumor types. Int. J. Cancer 111(5), 705-710 (2004).
91. Yazdi AS, Palmedo G, Flaig MJ et al. Mutations of the BRAF gene in benign and malignant melanocytic lesions. J. Invest. Dermatol. 121(5), 1160-1162 (2003).
92. Michaloglou C, Vredeveld LC, Soengas MS et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436(7051), 720-724 (2005).
93. Wellbrock C, Ogilvie L, Hedley D et al. V599EB-RAF is an oncogene in melanocytes. Cancer Res. 64(7), 2338-2342 (2004).
94. Sharpless NE, DePinho RA. Cancer: crime and punishment. Nature 436(7051), 636-637 (2005).
95. Wajapeyee N, Serra RW, Zhu X, Mahalingam M, Green MR. Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell 132(3), 363-374 (2008).
96. Chudnovsky Y, Adams AE, Robbins PB, Lin Q, Khavari PA. Use of human tissue to assess the oncogenic activity of melanoma-associated mutations. Nat. Genet. 37(7), 745-749 (2005).
97. Edlundh-Rose E, Egyhazi S, Omholt K et al. NRAS and BRAF mutations in melanoma tumours in relation to clinical characteristics: a study based on mutation screening by pyrosequencing. Melanoma Res. 16(6), 471-478 (2006).
98. Goel VK, Lazar AJ, Warneke CL, Redston MS, Haluska FG. Examination of mutations in BRAF, NRAS, and PTEN in primary cutaneous melanoma. J. Invest. Dermatol. 126(1), 154-160 (2006).
99. Jiveskog S, Ragnarsson-Olding B, Platz A, Ringborg U. N-ras mutations are common in melanomas from sun-exposed skin of humans but rare in mucosal membranes or unexposed skin. J. Invest. Dermatol. 111(5), 757-761 (1998).
100. Dumaz N, Hayward R, Martin J et al. In melanoma, RAS mutations are accompanied by switching signaling from BRAF to CRAF and disrupted cyclic AMP signaling. Cancer Res. 66(19), 9483-9491 (2006).
101. Kannengiesser C, Spatz A, Michiels S et al. Gene expression signature associated with BRAF mutations in human primary cutaneous melanomas. Mol. Oncol. 425-430 (2008).
102. Shields JM, Thomas NE, Cregger M et al. Lack of extracellular signal-regulated kinase mitogen-activated protein kinase signaling shows a new type of melanoma. Cancer Res. 67(4), 1502-1512 (2007).
103. Smalley KS, Xiao M, Villanueva J et al. CRAF inhibition induces apoptosis in melanoma cells with non-V600E BRAF mutations. Oncogene 28(1), 85-94 (2008).
104. Kortylewski M, Heinrich PC, Kauffmann ME et al. Mitogen-activated protein kinases control p27/Kip1 expression and growth of human melanoma cells. Biochem J. 357(Pt 1), 297-303 (2001).
105. Huntington JT, Shields JM, Der CJ 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. J. Biol. Chem. 279(32), 33168-33176 (2004).
106. McGill GG, Horstmann M, Widlund HR et al. Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability. Cell 109(6), 707-718 (2002).
107. Kwong L, Chin L, Wagner SN. Growth factors and oncogenes as targets in melanoma: lost in translation? Adv. Dermatol. 23, 99-129 (2007).
108. Dai DL, Martinka M, Li G. Prognostic significance of activated Akt expression in melanoma: a clinicopathologic study of 292 cases. J. Clin. Oncol. 23(7), 1473-1482 (2005).
109. Stahl JM, Sharma A, Cheung M et al. Deregulated Akt3 activity promotes development of malignant melanoma. Cancer Res. 64(19), 7002-7010 (2004).
110. Ross P, Hall L, Haff LA. Quantitative approach to single-nucleotide polymorphism analysis using MALDI-TOF mass spectrometry. Biotechniques 29(3), 620-626, 628-629 (2000).
111. Yoeli-Lerner M, Yiu GK, Rabinovitz I et al. Atk blocks breast cancer cell motility and invasion through the transcription factor NFAT. Mol. Cell 20, 539-550 (2005).
112. Bastian BC. Understanding the progression of melanocytic neoplasia using genomic analysis: from fields to cancer. Oncogene 22(20), 3081-3086 (2003).
113. Wu H, Goel V, Haluska FG. PTEN signaling pahtways in melanoma. Oncogene 22, 3113-3122 (2003).
114. Pollock PM, Walker GJ, Glendening JM et al. PTEN inactivation is rare in melanoma tumours but occurs frequently in melanoma cell lines. Melanoma Res. 12(6), 565-575 (2002).
115. Mikhail M, Velazquez E, Shapiro R et al. PTEN expression in melanoma: relationship with patient survival, Bcl-2 expression, and proliferation. Clin. Cancer Res. 11(14), 5153-5157 (2005).
116. Slipicevic A, Holm R, Nguyen MT et al. Expression of activated Akt and PTEN in malignant melanomas: relationship with clinical outcome. Am. J. Clin. Pathol. 124(4), 528-536 (2005).
117. Robertson GP, Furnari FB, Miele ME et al. In vitro loss of heterozygosity targets the PTEN/MMAC1 gene in melanoma. Proc. Natl Acad. Sci. USA 95(16), 9418-9423 (1998).
118. Stewart AL, Mhashilkar AM, Yang XH et al. PI3 kinase blockade by Ad-PTEN inhibits invasion and induces apoptosis in RGP and metastatic melanoma cells. Mol. Med. 8(8), 451-461 (2002).
119. Stahl JM, Cheung M, Sharma A et al. Loss of PTEN promotes tumor development in malignant melanoma. Cancer Res. 63(11), 2881-2890 (2003).
120. Robertson GP. Functional and therapeutic significance of Akt deregulation in malignant melanoma. Cancer Metastasis Rev. 24(2), 273-285 (2005).
121. You MJ, Castrillon DH, Bastian BC et al. Genetic analysis of Pten and Ink4a/Arf interactions in the suppression of tumorigenesis in mice. Proc. Natl Acad. Sci. USA 99, 1455-1460 (2002).
122. Di Cristofano A, Pesce B, Cordon-Cardo C, Pandolfi PP. Pten is essential for embryonic development and tumour suppression. Nat. Genet. 19(4), 348-355 (1998).
123. Stambolic V, Suzuki A, de la Pompa JL et al. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 95(1), 29-39 (1998).
124. Podsypanina K, Ellenson LH, Nemes A et al. Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems. Proc. Natl Acad. Sci. USA 96(4), 1563-1568 (1999).
125. Ma X, Ziel-van der Made AC, Autar B et al. Targeted biallelic inactivation of Pten in the mouse prostate leads to prostate cancer accompanied by increased epithelial cell proliferation but not by reduced apoptosis. Cancer Res. 65(13), 5730-5739 (2005).
126. Trotman LC, Wang X, Alimonti A et al. Ubiquitination regulates PTEN nuclear import and tumor suppression. Cell 128(1), 141-156 (2007).
127. Wang X, Trotman LC, Koppie T et al. NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN. Cell 128(1), 129-139 (2007).
128. Bedogni B, Welford SM, Kwan AC et al. Inhibition of phosphatidylinositol-3-kinase and mitogen-activated protein kinase kinase 1/2 prevents melanoma development and promotes melanoma regression in the transgenic TPRas mouse model. Mol. Cancer Ther. 5(12), 3071-3077 (2006).
129. Smalley KS, Haass NK, Brafford PA et al. Multiple signaling pathways must be targeted to overcome drug resistance in cell lines derived from melanoma metastases. Mol. Cancer Ther. 5(5), 1136-1144 (2006).
130. Tsao H, Goel V, Wu H, Yang G, Haluska FG. Genetic interaction between NRAS and BRAF mutations and PTEN/MMAC1 inactivation in melanoma. J. Invest. Dermatol. 122(2), 337-341 (2004).
131. Winnepenninckx V, Lazar V, Michiels S et al. Gene expression profiling of primary cutaneous melanoma and clinical outcome. J. Natl Cancer Inst. 98(7), 472-482 (2006).
132. Wellbrock C, Marais R. Elevated expression of MITF counteracts B-RAF-stimulated melanocyte and melanoma cell proliferation. J. Cell. Biol. 170(5), 703-708 (2005).
133. Wellbrock C, Rana S, Paterson H et al. Oncogenic BRAF regulates melanoma proliferation through the lineage speci?c factor MITF. PLoS ONE 3(7), e2734 (2008).
134. Garraway LA, Sellers WR. Lineage dependency and lineage-survival oncogenes in human cancer. Nat. Rev. Cancer 6(8), 593-602 (2006).
135. Hemesath TJ, Steingrimsson E, McGill G et al. Microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family. Genes Dev. 8(22), 2770-2780 (1994).
136. Steingrimsson E, Moore KJ, Lamoreux ML et al. Molecular basis of mouse microphthalmia (mi) mutations helps explain their developmental and phenotypic consequences. Nat. Genet. 8(3), 256-263 (1994).
137. Price ER, Fisher DE. Sensorineural deafness and pigmentation genes: melanocytes and the Mitf transcriptional network. Neuron 30(1), 15-18 (2001).
138. Weeraratna AT, Jiang Y, Hostetter G et al. Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell 1(3), 279-288 (2002).
139. Muthusamy V, Duraisamy S, Bradbury CM et al. Epigenetic silencing of novel tumor suppressors in malignant melanoma. Cancer Res. 66(23), 11187-11193 (2006).
140. Mori T, Martinez SR, O'Day SJ et al. Estrogen receptor-α methylation predicts melanoma progression. Cancer Res. 66(13), 6692-6698 (2006).
141. Mirmohammadsadegh A, Marini A, Nambiar S et al. Epigenetic silencing of the PTEN gene in melanoma. Cancer Res. 66(13), 6546-6552 (2006).
142. Kato Y, Salumbides BC, Wang X-F. Antitumor effect of the histone deacetylase inhibitor LAQ824 in combination with 13-cis-retinoic acid in human malignant melanoma. Mol. Cancer Ther. 6, 70-81 (2007).
143. Volinia S, Calin GA, Liu CG et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc. Natl Acad. Sci. USA 103(7), 2257-2261 (2006).
144. Gaur A, Jewell DA, Liang Y et al. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res. 67(6), 2456-2468 (2007).
145. Zhang L, Huang J, Yang N et al. MicroRNAs exhibit high frequency genomic alterations in human cancer. Proc. Natl Acad. Sci. USA 103(24), 9136-9141 (2006).
146. Kim M, Gans JD, Nogueira C et al. Comparative oncogenomics identifies NEDD9 as a melanoma metastasis gene. Cell 125(7), 1269-1281 (2006).
147. Maser RS, Choudhury B, Campbell PJ et al. Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers. Nature 447(7147), 966-971 (2007).