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Mechanisms of Oncogenesis pp 149–157Cite as

Carcinogenetic Pathway of Malignant Melanoma

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Part of the book series: Cancer Growth and Progression ((CAGP,volume 12))

Abstract

With an increasing incidence in the last decade, melanoma has become a significant public health concern worldwide. Melanoma is an aggressive disease that currently lacks effective treatment. The biology of melanoma is complex, with numerous different histologic subtypes, genetic predispositions, environmental factors, and clinical features though to play a role in carcinogenesis and outcome. The purpose of this chapter is to review the most recent advances in the tumorigenesis of melanoma focusing on photocarcinogenesis and the molecular pathways implicated in the development of this malignancy.

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References

  1. Geller AC, Swetter SM, Brooks K, Demierre M, Yaroch AL. Screening, early detection, and trends for melanoma: current status (2000–2006) and future directions. J Am Acad Dermatol 2007; 57(4):555–72.

    Article  PubMed  Google Scholar 

  2. Beral V, Evans S, Shaw H, Milton G. Cutaneous factors related to the risk of melanoma. Br J Dermatol 1983; 109:165–72.

    Article  PubMed  CAS  Google Scholar 

  3. Katsambas A, Nicolaidou E. Cutaneous malignant melanoma and sun exposure. Recent developments in epidemiology. Arch Dermatol 1996; 132:444–50.

    CAS  Google Scholar 

  4. Lew RA, Sober AJ, Cook N, Marvell R, Fitzpatrick TB. Sun exposure habits in patients with cutnaeous melanoma: a case control study. J Dermatol Surg Oncol 1983; 9:981–6.

    PubMed  CAS  Google Scholar 

  5. Schneider JS, Moore DH, Sagebiel RW. Risk factors for melanoma incidence in prospective follow-up. The importance of atypical (dysplastic) nevi. Arch Dermatol 1994; 130:1002–7.

    Article  CAS  Google Scholar 

  6. Kasiske BL, Danpanich E. Malignancies in renal transplant recipients. Transplant Proc 2000; 32:1499–500.

    Article  PubMed  CAS  Google Scholar 

  7. Ferrone CR, Ben Porat L, Panageas KS, Berwick M, Halpern AC, Patel A, et al. Clinicopathologic features of and risk factors for multiple primary melanomas. JAMA 2005; 294:1647–54.

    Article  PubMed  CAS  Google Scholar 

  8. Rosenberg CA, Greenland P, Khandekar J, Loar A, Ascensao J, Lopez AM. Association of nonmelanoma skin cancer with second malignancy. Cancer 2004; 100:130–8.

    Article  PubMed  Google Scholar 

  9. Mikkilineni R, Weinstock MA. Is the self-counting of moles a valid method of assessing melanoma risk? Arch Dermatol 2000; 136:1550–51.

    Article  PubMed  CAS  Google Scholar 

  10. Naldi L, Imberti GL, Parazzini F, Gallus S, La Vecchia C. Pigmentary traits, modalities of sun reaction, history of sunburns, and melanocytic nevi as risk factors for cutaneous malignant melanoma in the Italian population. Cancer 2000; 88:2703–10.

    Article  PubMed  CAS  Google Scholar 

  11. Grange F, Chompret A, Guilloud-Bataille M, Guillaume JC, Marqulis A, Prade M, et al. Comparison between familial and nonfamilial melanoma in France. Arch Dermatol 1995; 131:1154–59.

    Article  PubMed  CAS  Google Scholar 

  12. Luther U, Dichmann S, Schlobe A, Czech W, Norgauer J. UV light and skin cancer. Med Monatsschr Pharm 2000; 23:261.

    PubMed  CAS  Google Scholar 

  13. de Laat A, van Tilburg M, van der Leun JC, van Vloten WA, de Gruijl FR. Cell cycle kinetics following UVA irradiation in comparison to UVB and UVC irradiation. Photochem Photobiol 1996; 63:492.

    Article  PubMed  Google Scholar 

  14. de Gruijl FR, van der Leun JC. Physical variables in experimental photocarcinogenesis and quantitative relationships between stages of tumor development. Front Biosci 2002; 7:d1525.

    Article  PubMed  Google Scholar 

  15. Koh HK, Kligler BE, Lew RA. Sunlight and cutaneous malignant melanoma. Evidence for and against causation. Photochem Photobiol 1990; 51:765.

    CAS  Google Scholar 

  16. Holly EA, Aston DA, Cress RD, Ahn DK, Kristiansen JJ. Cutaneous melanoma in women. Exposure to sunlight, ability to tan, and other risk factors related to ultraviolet light. Am J Epidemiol 1995; 141:923.

    PubMed  CAS  Google Scholar 

  17. Autier P. Sunscreen and melanoma revisited. Arch Dermatol 2000; 136:423.

    Article  PubMed  CAS  Google Scholar 

  18. Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med 2005; 353(20):2135–47.

    Article  PubMed  CAS  Google Scholar 

  19. Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Devel 1999; 13:1501–12.

    Article  PubMed  CAS  Google Scholar 

  20. Kramer M, Stein B, Mai S, Kunz E, Konig H, Loferer H, et al. Radiation-induced activation of transcription factors in mammalian cells. Radiat Environ Biophys 1990; 29:303.

    Article  PubMed  CAS  Google Scholar 

  21. Hodges A, Smoller BR. Immunohistochemical comparison of p16 expression in actinic keratoses and squamous cell carcinomas of the skin. Mod Pathol 2002; 15:1121.

    Article  PubMed  Google Scholar 

  22. Sparrow LE, Eldon MJ, English DR, Heenan PJ. p16 and p21WAF1 protein expression in melanocytic tumors by immunohistochemistry. Am J Dermatopathol 1998; 20:255–61.

    Article  PubMed  CAS  Google Scholar 

  23. Hussein MR. Ultraviolet radiation and skin cancer: molecular mechanisms. J Cutan Pathol 2005; 32:191–205.

    Article  PubMed  Google Scholar 

  24. Hussein MR, Haemel AK, Wood GS. Apoptosis and melanoma: molecular mechanisms. J Pathol 2003; 199:275.

    Article  PubMed  CAS  Google Scholar 

  25. Spatz A, Giglia-Mari G, Benhammou S, Sarasin A. Association between DNA repair-deficiency and high level of p53 mutations in melanoma of xeroderma pigmentosum. Cancer Res 2001; 61:2480–6.

    PubMed  CAS  Google Scholar 

  26. Albino AP, Vidal MJ, McNutt NS, Shea CR, Prieto VG, Nanus DM, et al. Mutation and expression of p53 gene in human malignant melanoma. Melanoma Res 1994; 4:35–45.

    Article  PubMed  CAS  Google Scholar 

  27. Sander CS, Hamm F, Elsner P, Thiele JJ. Oxidative stress in malignant melanoma and non-melanoma skin cancer. Br J Dermatol 2003; 148:913–22.

    Article  PubMed  CAS  Google Scholar 

  28. Ortega S, Malumbres M, Barbacid M. Cyclin D-dependent kinases, INK4 inhibitors and cancer. Biochim Biophys Acta 2002; 1602:73–87.

    PubMed  CAS  Google Scholar 

  29. Hussussian CJ, Struewing JP, Goldstein AM, Higgins PA, Ally DS, Sheahan MD, et al. Germline p16 mutations in familial melanoma. Nat Genet 1994; 8:15–21.

    Article  PubMed  CAS  Google Scholar 

  30. Aitken J, Welch J, Duffy D, Milligan A, Green A, Martin N, et al. CDKN2A variants in a population-based sample of Queensland families with melanoma. J Natl Cancer Inst 1999; 91:446–52.

    Article  PubMed  CAS  Google Scholar 

  31. Tsao H, Zhang X, Kwitkiwski K, Finkelstein DM, Sober AJ, Haluska FG. Low prevalence of germline CDKN2A and CDK4 mutations in patients with early-onset melanoma. Arch Dermatol 2000; 136:1118–22.

    Article  PubMed  CAS  Google Scholar 

  32. Funk JO, Schiller PI, Barrett MT, Wong DJ, Kind P, Sander CA. p16INK4a expression is frequently decreased and associated with 9p21 loss of heterozygosity in sporadic melanoma. J Cut Pathol 1998; 25:291–6.

    Article  CAS  Google Scholar 

  33. van der Velden PA, Metzelaar-Blok JA, Bergaman W, Monique H, Hurks H, Frants RR, et al. Promoter hypermethylation: a common cause of reduced p16(INK4a) expression in uveal melanoma. Cancer Res 2001; 61:5303–6.

    PubMed  Google Scholar 

  34. Peng HQ, Bailey D, Bronson D, Goss PE, Hogg D. Loss of heterozygosity of tumor suppressor genes in testis cancer. Can Res 1995; 55:2871–5.

    CAS  Google Scholar 

  35. Matsumura Y, Nishigori C, Yagi T, Imamura S, Takebe H. Mutations of p16 and p15 tumor suppressor genes and replication errors contribute independently to the pathogenesis of sporadic malignant melanoma. Arch Dermatol Res 1998; 290:175–80.

    Article  PubMed  CAS  Google Scholar 

  36. Reed JA, Loganzo F Jr, Shea CR, Walker GJ, Flores JF, Glendening JM, et al. Loss of expression of the p16/cyclin-dependent kinase inhibitor 2 tumor suppressor gene in melanocytic lesions correlates with invasive stage of tumor progression. Cancer Res 1995; 55:2713–8.

    PubMed  CAS  Google Scholar 

  37. Keller-Melchior R, Schmidt R, Piepkorn M. Expression of the tumor suppressor gene product p16INK4 in benign and malignant melanocytic lesions. J Invest Dermatol 1998; 110:932–8.

    Article  PubMed  CAS  Google Scholar 

  38. Winnepenninckx V, van den Oord JJ. p16INK4A expression in malignant melanomas with or without a contiguous naevus remnant: a clue to their divergent pathogenesis? Melanoma Res 2004; 14:321–2.

    Article  PubMed  CAS  Google Scholar 

  39. Pavey SJ, Cummings MC, Whiteman DC, Castellano M, Walsh MD, Gabrielli BG, et al. Loss of p16 expression is associated with histological features of melanoma invasion. Melanoma Res 2002; 12:539–47.

    Article  PubMed  CAS  Google Scholar 

  40. Talve L, Sauroja I, Collan Y, Punnonen K, Ekfors T. Loss of expression of the p16INK4/CDKN2 gene in cutaneous malignant melanoma correlates with tumor cell proliferation and invasive stage. Int J Cancer 1997; 74:255–9.

    Article  PubMed  CAS  Google Scholar 

  41. Straume O, Akslen LA. Alterations and prognostic significance of p16 and p53 protein expression in subgroups of cutaneous melanoma. Int J Cancer 1997; 74:535–9.

    Article  PubMed  CAS  Google Scholar 

  42. Darnton SJ. Demystified…p53. Mol Pathol 1998; 51:248–53.

    Article  PubMed  CAS  Google Scholar 

  43. Lubbe J, Reichel M, Burg G, Kleihues P. Absence of p53 gene mutations in cutaneous melanoma. J Invest Dermatol 1994; 102:819–21.

    Article  PubMed  CAS  Google Scholar 

  44. Soto JL, Cabrera CM, Serrano S, Lopez-Nevot MA. Mutation analysis of genes that control the G1/S cell cycle in melanoma: TP53, CDKN1A, CDKN2A, and CDKN2B. BMC Cancer 2005; 5:36.

    Article  PubMed  CAS  Google Scholar 

  45. Ragnarsso-Olding BK, Karsberg S, Platz A, Ringborq UK. Mutations in the TP53 gene in human malignant melanomas derived from sun-exposed skin and unexposed mucosal membranes. Melanoma Res 2002; 12:453–63.

    Article  Google Scholar 

  46. Sparrow LE, Soong R, Dawkins HJ, Iacopetta BJ, Heenan PJ. p53 gene mutation and expression in naevi and melanomas. Melanoma Res 1995; 5:93–100.

    Article  PubMed  CAS  Google Scholar 

  47. Li W, Sanki A, Karim RZ, Thompson JF, Lee CS, Zhuang L, et al. The role of cell cycle regulatory proteins in the pathogenesis of melanoma. Pathol 2006; 38:287–301.

    Article  CAS  Google Scholar 

  48. Lassam NJ, From L, Kahn HJ. Overexpression of p53 is a late event in the development of malignant melanoma. Cancer Res 1993; 53:2235–8.

    PubMed  CAS  Google Scholar 

  49. Ross DA, Wilson GD. Flow cytometric analysis of p53 oncoprotein expression in cutaneous melanoma. Br J Surg 1997; 84; 803–7.

    Article  PubMed  CAS  Google Scholar 

  50. Flores VA, Holm R, Fodstad O. Accumulation of p53 protein in human malignant melanoma. Relationship to clinical outcome. Melanoma Res 1995; 5:183–7.

    Google Scholar 

  51. Yamamoto M, Takahashi H, Saitoh K, Horikoshi T, Takahashi M. Expression of the p53 protein in malignant melanoma as a prognostic indicator. Arch Dermatol Res 1995; 287:146–51.

    Article  PubMed  CAS  Google Scholar 

  52. Wehrle-Haller B, Weston JA. Altered cell-surface targeting of stem cell factor causes loss of melanocyte precursors in steel17H mutant mice. Dev Biol 1999; 210:71.

    Article  PubMed  CAS  Google Scholar 

  53. Welker P, Schadendorf D, Artue M, Grabbe J, Henz BM. Expression of SCF splice variants in human melanocytes and melanoma cell lines: potential prognostic implications. Br J Cancer 2000; 82:1453.

    PubMed  CAS  Google Scholar 

  54. Imokawa G. Autocrine and paracrine regulation of melanocytes in human skin and in pigmentary disorders. Pigment Cell Res 2004; 17:96.

    Article  PubMed  CAS  Google Scholar 

  55. Montone KT, van Belle P, Elenitsas R, Elder DE. Proto-oncogene c-kit expression in malignant melanoma: protein loss with tumor progression. Mod Pathol 1997; 10:939–44.

    PubMed  CAS  Google Scholar 

  56. Janku F, Novotny J, Julis I, Julisova I, Pecen L, Tomancova V, et al. KIT receptor expressed in more than 50% of early-stage malignant melanoma: a retrospective study of 261 patients. Melanoma Res 2005; 15:251–6.

    Article  PubMed  CAS  Google Scholar 

  57. Curtin JA, Busam K, Pinkel D, Bastian BC. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol 2006; 24:4340–6.

    Article  PubMed  CAS  Google Scholar 

  58. Wyman K, Atkins MB, Prieto V, Eton O, McDermott DF, Hubbard F, et al. Multicenter phase II trial of high-dose imatinib mesylate in metastatic melanoma. Cancer 2006; 106:2005–11.

    Article  PubMed  CAS  Google Scholar 

  59. Rakosy Z, Vizkeleti L, Ecsedi S, Voko Z, Begany A, Barok M, et al. EGFR gene copy number alterations in primary cutaneous malignant melanomas are associated with poor prognosis. Int J Cancer 2007; 121:1729–37.

    Article  PubMed  CAS  Google Scholar 

  60. de Wit PE, Moretti S, Koenders PG, Weterman MA, van Muijen GN, Gianotti B, et al. Increasing epidermal growth factor receptor expression in human melanocytic tumor progression. J Invest Dermatol 1992; 99:168–73.

    Article  PubMed  Google Scholar 

  61. Stove C, Stove V, Derycke L, Van Marck V, Mareel M, Bracke M. The heregulin/human epidermal growth factor receptor as a new growth factor system in melanoma with multiple ways of deregulation. J Invest Dermatol 2003; 121:802–12.

    Article  PubMed  CAS  Google Scholar 

  62. Bartek J, Bartkova J, Lukas J. The retinoblastoma protein pathway and the restriction point. Curr Opin Cell Biol 1996; 8:805–14.

    Article  PubMed  CAS  Google Scholar 

  63. Utikal J, Udart M, Leiter U, Peter RU, Krahn G. Additional cyclin D(1) gene copies associated with chromosome 11 aberrations in cutaneous malignant melanoma. Int J Oncol 2005; 26:597–605.

    PubMed  CAS  Google Scholar 

  64. Bastian BC, Kashani-Sabet M, Hamm H, Godfrey T, Moore DH 2nd, Brocker EB, et al. Gene amplification characterize acral melanoma and permit the detection of occult tumor cells in the surrounding skin. Cancer Res 2000; 60:1968–73.

    PubMed  CAS  Google Scholar 

  65. Maelandsmo GM, Florenes VA, Hovig E, Oyjord T, Engebraaten O, Holm R, et al. Involvement of the pRb/p16/cdk4/cyclin D1 pathway in the tumorigenesis of sporadic malignant melanomas. Br J Cancer 1996; 73:909–16.

    PubMed  CAS  Google Scholar 

  66. Sauter ER, Yeo UC, von Stemm A, Zhu W, Litwin S, Tichansky DS, et al. Cyclin D1 is a candidate oncogene in cutaneous melanoma. Cancer Res 2002; 62:3200–6.

    PubMed  CAS  Google Scholar 

  67. Errico ME, Staibano S, Tranfa F, Bonavolonta G, Lo Muzio L, Somma P, et al. Expression of cyclin-D1 in uveal malignant melanoma. Anticancer Res 2003; 23:2701–6.

    PubMed  Google Scholar 

  68. Florenes VA, Faye RS, Maelandsmo GM, Nesland JM, Holm R. Levels of cyclin D1 and D3 in malignant melanoma: deregulated cyclin D3 expression is associated with poor clinical outcome in superficial melanoma. Clin Cancer Res 2000; 6:3614–20.

    PubMed  CAS  Google Scholar 

  69. Blackburn EH. Structure and function of telomeres. Nature 1991; 350:569.

    Article  PubMed  CAS  Google Scholar 

  70. Ramirez RD, D’Atri S, Pagani E, Faraggiana T, Lacal PM, Taylor RS, et al. Progressive increase in telomerase activity from benign melanocytic conditions to malignant melanoma. Neoplasia 1999; 1:42.

    Article  PubMed  CAS  Google Scholar 

  71. Fullen DR, Weijian Z, Dafydd T, Lyndon DS. HTERT expression in melanocytic lesions: an immunohistochemical study on paraffin-embedded tissue. J Cutan Pathol 2005; 32:680–4.

    Article  PubMed  Google Scholar 

  72. Guttman-Yassky E, Bergman R, Manov L, Sprecher E, Shaefer Y, Kerner H. Human telomerase RNA component expression in Spitz nevi, common melanocytic nevi, and malignant melanoma. J Cutan Pathol 2002; 29:341.

    Article  PubMed  Google Scholar 

  73. Bastian BC. Hypothesis: a role for telomere crisis in spontaneous regression of melanoma. Arch Dermatol 2003; 139:667–8.

    Article  PubMed  Google Scholar 

  74. Papp T, Pemsel H, Zimmermann R, Bastrop R, Weiss DG, Schiffmann D. Mutational analysis of the N-ras, p53, p16INK4a, CDK4, and MC1R genes in human congenital melanocytic naevi. J Med Genet 1999; 36:610–14.

    PubMed  CAS  Google Scholar 

  75. Demunter A, Stas M, Degreef H, De Wolf-Peeters C, van den Oord JJ. Analysis of N- and K-ras mutations in distinctive tumor progression phases of melanoma. J Invest Dermatol 2001; 117:1483–9.

    Article  PubMed  CAS  Google Scholar 

  76. Jafari M, Papp T, Kirchner S, Diener U, Henschler D, Burg G, 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 1995; 121:23–30.

    Article  PubMed  CAS  Google Scholar 

  77. van Elsas A, Zerp SF, van der Flier S, Kruse KM, Aarnoudse C, Hayward NK, et al. Relevance of ultraviolet-induced N-ras oncogene point mutations in development of primary human cutaneous melanoma. Am J Pathol 1996; 149:883–93.

    PubMed  Google Scholar 

  78. Bastian BC, LeBoit PE, Pinkel D. Mutations and copy number increase of HRAS in Spitz nevi with distinctive histopathologic features. Am J Pathol 2000; 157:967–72.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology and Cell Biology, College of Medicine, University of South Florida, Tampa, FL, USA

    Kenneth B. Calder

  2. Pathology and Dermatology, James A. Haley VA Hospital, College of Medicine, University of South Florida, Tampa, FL, USA

    Michael B. Morgan

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  1. Kenneth B. Calder
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  2. Michael B. Morgan
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Correspondence to Kenneth B. Calder .

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Editors and Affiliations

  1. Research Institute, H. Lee Moffitt Cancer Center &, Magnolia Drive 12902, Tampa, 33612, USA

    Domenico Coppola

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Calder, K.B., Morgan, M.B. (2010). Carcinogenetic Pathway of Malignant Melanoma. In: Coppola, D. (eds) Mechanisms of Oncogenesis. Cancer Growth and Progression, vol 12. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3725-1_9

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  • DOI: https://doi.org/10.1007/978-90-481-3725-1_9

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