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Nevogenesis pp 127-135 | Cite as

Genes and Nevogenesis

  • Stephen W. DuszaEmail author
  • Mark E. Burnett
Chapter
  • 453 Downloads

Abstract

Total nevus count has been shown to be a strong and consistent predictor of melanoma risk in adult population [1]. Twin studies have been a tremendously useful tool to tease out the relative contributions of genetic and behavioral risk factors for disease. Exploring differences between monozygotic and dizygotic twin pairs allows for the assessment of the relative contribution of genetic and environmental factors for a specific trait. Several twin cohorts have been assembled to assess the roles of genetics and UVR in nevus phenotype. In general, total nevus counts have been shown to be highly influenced by genetic factors. Twin studies have estimated that up to 60 % of the variation in nevus counts can be attributed to genetic factor [2–4]. One of the first studies to evaluate nevus phenotype in twins found that in 23 monozygotic (MZ) and 22 dizygotic (DZ) twin pairs, a strong correlation (r = 0.83) for total body nevus counts was found in the monozygotic twins. However, when assessing the dizygotic twins, the correlation disappeared (r = −0.24) [3]. In a parallel study exploring a larger cohort of 221 twin pairs, the intraclass correlation for total nevus count in MZ pairs was 0.94 (95% CI, 0.92–0.96) compared with 0.63 (0.52–0.74) for the DZ pairs [5]. These results were corroborated in a study by Goldgar et al. in a cohort of kindreds selected from dysplastic nevus syndrome and melanoma families. Investigators found that total nevus number (TNN) and total nevus density (TND) were highly correlated within families [6]. Parameter estimates from the best-fitting genetic model indicated that a major gene may be responsible for 55% of the phenotypic variability of TND in kindreds. Further investigations utilizing genome-wide association studies suggest that variants on 9p and 22q harbor genes associated with increased nevus counts [7]. In addition, the exploration of other genes associated with pigmentation, such as the melanocortin-1 receptor (MC1R) and OCA2, may provide additional insights for nevus development. To date, a “nevus gene” has not been identified, but as with many other characteristics, nevi are most likely polygenic, with many individual genes working in concert to determine an individual’s overall nevus phenotype.

Keywords

BRAF Mutation BRAF V600E Mutation Melanoma Risk Dysplastic Nevus Oculocutaneous Albinism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Funding Source

None.

Conflict of Interest

None.

References

  1. 1.
    Gandini S, Sera F, Cattaruzza MS, Pasquini P, Abeni D, Boyle P, Melchi CF. Meta-analysis of risk factors for cutaneous melanoma: I. Common and atypical naevi. Eur J Cancer. 2005;41(1):28–44.PubMedGoogle Scholar
  2. 2.
    Bataille V. Genetics of familial and sporadic melanoma. Clin Exp Dermatol. 2000;25(6):464–70.PubMedGoogle Scholar
  3. 3.
    Easton DF, Cox GM, Macdonald AM, Ponder BA. Genetic susceptibility to naevi – a twin study. Br J Cancer. 1991;64(6):1164–7.PubMedGoogle Scholar
  4. 4.
    Zhu G, Duffy DL, Eldridge A, Grace M, Mayne C, O’Gorman L, et al. A major quantitative-trait locus for mole density is linked to the familial melanoma gene CDKN2A: a maximum-likelihood combined linkage and association analysis in twins and their sibs. Am J Hum Genet. 1999;65(2):483–92.PubMedGoogle Scholar
  5. 5.
    Wachsmuth RC, Gaut RM, Barrett JH, Saunders CL, Randerson-Moor JA, Eldridge A. Heritability and gene-environment interactions for melanocytic nevus density examined in a U.K. adolescent twin study. J Invest Dermatol. 2001;117(2):348–52.PubMedGoogle Scholar
  6. 6.
    Goldgar DE, Cannon-Albright LA, Meyer LJ, Piepkorn MW, Zone JJ, Skolnick MH. Inheritance of nevus number and size in melanoma and dysplastic nevus syndrome kindreds. J Natl Cancer Inst. 1991;83(23):1726–33.PubMedGoogle Scholar
  7. 7.
    Falchi M, Bataille V, Hayward NK, Duffy DL, Bishop JA, Pastinen T, et al. Genome-wide association study identifies variants at 9p21 and 22q13 associated with development of cutaneous nevi. Nat Genet. 2009;41(8):915–9.PubMedGoogle Scholar
  8. 8.
    de Snoo FA, Hayward NK. Cutaneous melanoma susceptibility and progression genes. Cancer Lett. 2005;230(2):153–86.PubMedGoogle Scholar
  9. 9.
    de Snoo FA, Hottenga JJ, Gillanders EM, Sandkuijl LA, Jones MP, Bergman W, et al. Genome-wide linkage scan for atypical nevi in p16-Leiden melanoma families. Eur J Hum Genet. 2008;16(9):1135–41.PubMedGoogle Scholar
  10. 10.
    Bates S, Bonetta L, MacAllan D, Parry D, Holder A, Dickson C, et al. CDK6 (PLSTIRE) and CDK4 (PSK-J3) are a distinct subset of the cyclin-dependent kinases that associate with cyclin D1. Oncogene. 1994;9(1):71–9.PubMedGoogle Scholar
  11. 11.
    Falchi M, Spector TD, Perks U, Kato BS, Bataille V. Genome-wide search for nevus density shows linkage to two melanoma loci on chromosome 9 and identifies a new QTL on 5q31 in an adult twin cohort. Hum Mol Genet. 2006;15(20):2975–9.PubMedGoogle Scholar
  12. 12.
    Zhu G, Montgomery GW, James MR, Trent JM, Hayward NK, Martin NG, et al. A genome-wide scan for naevus count: linkage to CDKN2A and to other chromosome regions. Eur J Hum Genet. 2007;15(1):94–102.PubMedGoogle Scholar
  13. 13.
    Goldstein AM, Struewing JP, Chidambaram A, Fraser MC, Tucker MA. Genotype-phenotype relationships in U.S. melanoma-prone families with CDKN2A and CDK4 mutations. J Natl Cancer Inst. 2000;92(12):1006–10.PubMedGoogle Scholar
  14. 14.
    Soufir N, Avril MF, Chompret A, Demenais F, Bombled J, Spatz A, et al. Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France. The French Familial Melanoma Study Group. Hum Mol Genet. 1998;7(2):209–16.PubMedGoogle Scholar
  15. 15.
    Lin JY, Fisher DE. Melanocyte biology and skin pigmentation. Nature. 2007;445(7130):843–50.PubMedGoogle Scholar
  16. 16.
    Tsatmali M, Ancans J, Yukitake J, Thody AJ. Skin POMC peptides: their actions at the human MC-1 receptor and roles in the tanning response. Pigment Cell Res. 2000;13 Suppl 8:125–9.PubMedGoogle Scholar
  17. 17.
    Westerhof W. The discovery of the human melanocyte. Pigment Cell Res. 2006;19(3):183–93.PubMedGoogle Scholar
  18. 18.
    Rouzaud F, Kadekaro AL, Abdel-Malek ZA, Hearing VJ. MC1R and the response of melanocytes to ultraviolet radiation. Mutat Res. 2005;571(1–2):133–52, 122–52.PubMedGoogle Scholar
  19. 19.
    Valverde P, Healy E, Jackson I, Rees JL, Thody AJ. Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans. Nat Genet. 1995;11(3):328–30.PubMedGoogle Scholar
  20. 20.
    Kanetsky PA, Rebbeck TR, Hummer AJ, Panossian S, Armstrong BK, Kricker A, et al. Population-based study of natural variation in the melanocortin-1 receptor gene and melanoma. Cancer Res. 2006;66(18):9330–7.PubMedGoogle Scholar
  21. 21.
    Landi MT, Bauer J, Pfeiffer RM, Elder DE, Hulley B, Minghetti P, et al. MC1R germline variants confer risk for BRAF-mutant melanoma. Science. 2006;313(5786):521–2.PubMedGoogle Scholar
  22. 22.
    Landi MT, Kanetsky PA, Tsang S, Gold B, Munroe D, Rebbeck T, et al. MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean population. J Natl Cancer Inst. 2005;97(13):998–1007.PubMedGoogle Scholar
  23. 23.
    Yamaguchi Y, Takahashi K, Zmudzka BZ, Kornhauser A, Miller SA, Tadokoro T, et al. Human skin responses to UV radiation: pigment in the upper epidermis protects against DNA damage in the lower epidermis and facilitates apoptosis. FASEB J. 2006;20(9):1486–8.PubMedGoogle Scholar
  24. 24.
    Barker D, Dixon K, Medrano EE, Smalara D, Im S, Mitchell D, et al. Comparison of the responses of human melanocytes with different melanin contents to ultraviolet B irradiation. Cancer Res. 1995;55(18):4041–6.PubMedGoogle Scholar
  25. 25.
    Suzuki I, Cone RD, Im S, Nordlund J, Abdel-Malek ZA. Binding of melanotropic hormones to the melanocortin receptor MC1R on human melanocytes stimulates proliferation and melanogenesis. Endocrinology. 1996;137(5):1627–33.PubMedGoogle Scholar
  26. 26.
    Gerstenblith MR, Goldstein AM, Fargnoli MC, Peris K, Landi MT. Comprehensive evaluation of allele frequency differences of MC1R variants across populations. Hum Mutat. 2007;28(5):495–505.PubMedGoogle Scholar
  27. 27.
    Savage SA, Gerstenblith MR, Goldstein AM, Mirabello L, Fargnoli MC, Peris K, et al. Nucleotide diversity and population differentiation of the melanocortin 1 receptor gene, MC1R. BMC Genet. 2008;9:31.PubMedGoogle Scholar
  28. 28.
    Sturm RA. Skin colour and skin cancer – MC1R, the genetic link. Melanoma Res. 2002;12(5):405–16.PubMedGoogle Scholar
  29. 29.
    Raimondi S, Sera F, Gandini S, Iodice S, Caini S, Maisonneuve P, et al. MC1R variants, melanoma and red hair color phenotype: a meta-analysis. Int J Cancer. 2008;122(12):2753–60.PubMedGoogle Scholar
  30. 30.
    Papp T, Pemsel H, Rollwitz I, Schipper H, Weiss DG, Schiffmann D, et al. Mutational analysis of N-ras, p53, CDKN2A (p16(INK4a)), p14(ARF), CDK4, and MC1R genes in human dysplastic melanocytic naevi. J Med Genet. 2003;40(2):E14.PubMedGoogle Scholar
  31. 31.
    Gibbs P, Brady BM, Robinson WA. The genes and genetics of malignant melanoma. J Cutan Med Surg. 2002;6(3):229–35.PubMedGoogle Scholar
  32. 32.
    Kim RD, Curtin JA, Bastian BC. Lack of somatic alterations of MC1R in primary melanoma. Pigment Cell Melanoma Res. 2008;21(5):579–82.PubMedGoogle Scholar
  33. 33.
    Chaudru V, Laud K, Avril MF, Miniere A, Chompret A, Bressac-de Paillerets B. Melanocortin-1 receptor (MC1R) gene variants and dysplastic nevi modify penetrance of CDKN2A mutations in French melanoma-prone pedigrees. Cancer Epidemiol Biomarkers Prev. 2005;14(10):2384–90.PubMedGoogle Scholar
  34. 34.
    Hoiom V, Tuominen R, Kaller M, Linden D, Ahmadian A, Mansson-Brahme E, et al. MC1R variation and melanoma risk in the Swedish population in relation to clinical and pathological parameters. Pigment Cell Melanoma Res. 2009;22(2):196–204.PubMedGoogle Scholar
  35. 35.
    Zhu G, Evans DM, Duffy DL, Montgomery GW, Medland SE, Gillespie NA, et al. A genome scan for eye color in 502 twin families: most variation is due to a QTL on chromosome 15q. Twin Res. 2004;7(2):197–210.PubMedGoogle Scholar
  36. 36.
    Duffy DL, Montgomery GW, Chen W, Zhao ZZ, Le L, James MR, et al. A three-single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation. Am J Hum Genet. 2007;80(2):241–52.PubMedGoogle Scholar
  37. 37.
    Schacter B, Lederman MM, LeVine MJ, Ellner JJ. Ultraviolet radiation inhibits human natural killer activity and lymphocyte proliferation. J Immunol. 1983;130(5):2484–7.PubMedGoogle Scholar
  38. 38.
    Weitzen ML, Bonavida B. Mechanism of inhibition of human natural killer activity by ultraviolet radiation. J Immunol. 1984;133(6):3128–32.PubMedGoogle Scholar
  39. 39.
    Cooper KD, Oberhelman L, Hamilton TA, Baadsgaard O, Terhune M, LeVee G, et al. UV exposure reduces immunization rates and promotes tolerance to epicutaneous antigens in humans: relationship to dose, CD1a-DR  +  epidermal macrophage induction, and Langerhans cell depletion. Proc Natl Acad Sci USA. 1992;89(18):8497–501.PubMedGoogle Scholar
  40. 40.
    Nakagawa S, Koomen CW, Bos JD, Teunissen MB. Differential modulation of human epidermal Langerhans cell maturation by ultraviolet B radiation. J Immunol. 1999;163(10):5192–200.PubMedGoogle Scholar
  41. 41.
    Schwarz T. Photoimmunosuppression. Photodermatol Photoimmunol Photomed. 2002;18(3):141–5.PubMedGoogle Scholar
  42. 42.
    Parrish JA. Immunosuppression, skin cancer, and ultraviolet A radiation. N Engl J Med. 2005;353(25):2712–3.PubMedGoogle Scholar
  43. 43.
    Li-Weber M, Treiber MK, Giaisi M, Palfi K, Stephan N, Parg S, et al. Ultraviolet irradiation suppresses T cell activation via blocking TCR-mediated ERK and NF-kappa B signaling pathways. J Immunol. 2005;175(4):2132–43.PubMedGoogle Scholar
  44. 44.
    Hanneman KK, Cooper KD, Baron ED. Ultraviolet immunosuppression: mechanisms and consequences. Dermatol Clin. 2006;24(1):19–25.PubMedGoogle Scholar
  45. 45.
    Schwarz T. 25 years of UV-induced immunosuppression mediated by T cells-from disregarded T suppressor cells to highly respected regulatory T cells. Photochem Photobiol. 2008;84(1):10–8.PubMedGoogle Scholar
  46. 46.
    Schwarz T. The dark and the sunny sides of UVR-induced immunosuppression: photoimmunology revisited. J Invest Dermatol. 2010;130(1):49–54.PubMedGoogle Scholar
  47. 47.
    Damian DL, Matthews YJ, Phan TA, Halliday GM. An action spectrum for ultraviolet radiation-induced immunosuppression in humans. Br J Dermatol. 2011;164(3):657–9.PubMedGoogle Scholar
  48. 48.
    Hutchinson J. Outbreak of a large crop of pigmented moles: remarks as to possible connection with melanosis. J Cutan Med Dis Skin. 1868;1:170–1.Google Scholar
  49. 49.
    Bong HW, Lee SJ, Lee KH, Chung KY. Disseminated eruptive nevocellular nevi. J Dermatol. 1995;22(4):292–7.PubMedGoogle Scholar
  50. 50.
    Kopf AW, Grupper C, Baer RL, Mitchell JC. Eruptive nevocytic nevi after severe bullous disease. Arch Dermatol. 1977;113(8):1080–4.PubMedGoogle Scholar
  51. 51.
    Kirby JD, Darley CR. Eruptive melanocytic naevi following severe bullous disease. Br J Dermatol. 1978;99(5):575–80.PubMedGoogle Scholar
  52. 52.
    Goerz G, Tsambaos D. Eruptive nevocytic nevi after Lyell’s syndrome. Arch Dermatol. 1978;114(9):1400–1.PubMedGoogle Scholar
  53. 53.
    Bauer JW, Schaeppi H, Kaserer C, Hantich B, Hintner H. Large melanocytic nevi in hereditary epidermolysis bullosa. J Am Acad Dermatol. 2001;44(4):577–84.PubMedGoogle Scholar
  54. 54.
    Lanschuetzer CM, Emberger M, Hametner R, Klausegger A, Pohla-Gubo G, Hintner H, et al. Pathogenic mechanisms in epidermolysis bullosa naevi. Acta Derm Venereol. 2003;83(5):332–7.PubMedGoogle Scholar
  55. 55.
    Greene MH, Young TI, Clark Jr WH. Malignant melanoma in renal-transplant recipients. Lancet. 1981;1(8231):1196–9.PubMedGoogle Scholar
  56. 56.
    Duvic M, Lowe L, Rapini RP, Rodriguez S, Levy ML. Eruptive dysplastic nevi associated with human immunodeficiency virus infection. Arch Dermatol. 1989;125(3):397–401.PubMedGoogle Scholar
  57. 57.
    Barker JN, MacDonald DM. Eruptive dysplastic naevi following renal transplantation. Clin Exp Dermatol. 1988;13(2):123–5.PubMedGoogle Scholar
  58. 58.
    Hughes BR, Cunliffe WJ, Bailey CC. Excess benign melanocytic naevi after chemotherapy for malignancy in childhood. BMJ. 1989;299(6691):88–91.PubMedGoogle Scholar
  59. 59.
    de Wit PE, de Vaan GA, de Boo TM, Lemmens WA, Rampen FH. Prevalence of naevocytic naevi after chemotherapy for childhood cancer. Med Pediatr Oncol. 1990;18(4):336–8.PubMedGoogle Scholar
  60. 60.
    McGregor JM, Barker JN, MacDonald DM. The development of excess numbers of melanocytic naevi in an immunosuppressed identical twin. Clin Exp Dermatol. 1991;16(2):131–2.PubMedGoogle Scholar
  61. 61.
    Betlloch I, Amador C, Chiner E, Pasquau F, Calpe JL, Vilar A. Eruptive melanocytic nevi in human immunodeficiency virus infection. Int J Dermatol. 1991;30(4):303.PubMedGoogle Scholar
  62. 62.
    Smith CH, McGregor JM, Barker JN, Morris RW, Rigden SP, MacDonald DM. Excess melanocytic nevi in children with renal allografts. J Am Acad Dermatol. 1993;28(1):51–5.PubMedGoogle Scholar
  63. 63.
    Richert S, Bloom EJ, Flynn K, Seraly MP. Widespread eruptive dermal and atypical melanocytic nevi in association with chronic myelocytic leukemia: case report and review of the literature. J Am Acad Dermatol. 1996;35(2 Pt 2):326–9.PubMedGoogle Scholar
  64. 64.
    Karrer S, Szeimies RM, Stolz W, Landthaler M. Eruptive melanocytic nevi after chemotherapy. Klin Padiatr. 1998;210(1):43–6.PubMedGoogle Scholar
  65. 65.
    Firooz A, Komeili A, Dowlati Y. Eruptive melanocytic nevi and cherry angiomas secondary to exposure to sulfur mustard gas. J Am Acad Dermatol. 1999;40(4):646–7.PubMedGoogle Scholar
  66. 66.
    Bogenrieder T, Weitzel C, Scholmerich J, Landthaler M, Stolz W. Eruptive multiple lentigo-maligna-like lesions in a patient undergoing chemotherapy with an oral 5-fluorouracil prodrug for metastasizing colorectal carcinoma: a lesson for the pathogenesis of malignant melanoma? Dermatology. 2002;205(2):174–5.PubMedGoogle Scholar
  67. 67.
    Alaibac M, Piaserico S, Rossi CR, Foletto M, Zacchello G, Carli P, et al. Eruptive melanocytic nevi in patients with renal allografts: report of 10 cases with dermoscopic findings. J Am Acad Dermatol. 2003;49(6):1020–2.PubMedGoogle Scholar
  68. 68.
    Belloni Fortina A, Piaserico S, Zattra E, Alaibac M. Dermoscopic features of eruptive melanocytic naevi in an adult patient receiving immunosuppressive therapy for Crohn’s disease. Melanoma Res. 2005;15(3):223–4.PubMedGoogle Scholar
  69. 69.
    Martin Hernandez JM, Donat Colomer J, Monteagudo Castro C, Fernandez-Delgado Cerda R, Alonso Usero V, Jorda Cuevas E. Acral eruptive nevi after chemotherapy in children with acute lymphoblastic leukemia. An Pediatr (Barc). 2006;65(3):260–2.Google Scholar
  70. 70.
    Piaserico S, Alaibac M, Fortina AB, Peserico A. Clinical and dermatoscopic fading of post-transplant eruptive melanocytic nevi after suspension of immunosuppressive therapy. J Am Acad Dermatol. 2006;54(2):338–40.PubMedGoogle Scholar
  71. 71.
    Binder B, Ahlgrimm-Siess V, Hofmann-Wellenhof R. Eruptive melanocytic nevi of the palms and soles in a patient with Crohn disease. J Dtsch Dermatol Ges. 2006;4(6):486–8.PubMedGoogle Scholar
  72. 72.
    Bovenschen HJ, Tjioe M, Vermaat H, de Hoop D, Witteman BM, Janssens RW, et al. Induction of eruptive benign melanocytic naevi by immune suppressive agents, including biologicals. Br J Dermatol. 2006;154(5):880–4.PubMedGoogle Scholar
  73. 73.
    Reutter JC, Long EM, Morrell DS, Thomas NE, Groben PA. Eruptive post-chemotherapy in situ melanomas and dysplastic nevi. Pediatr Dermatol. 2007;24(2):135–7.PubMedGoogle Scholar
  74. 74.
    Deslandres M, Sibaud V, Chevreau C, Delord JP. Cutaneous side effects associated with epidermal growth factor receptor and tyrosine kinase inhibitors. Ann Dermatol Venereol. 2008;1:16–24.Google Scholar
  75. 75.
    Bennani-Lahlou M, Mateus C, Escudier B, Massard C, Soria JC, Spatz A, et al. Eruptive nevi associated with sorafenib treatment. Ann Dermatol Venereol. 2008;135(10):672–4.PubMedGoogle Scholar
  76. 76.
    Robert C, Mateus C, Spatz A, Wechsler J, Escudier B. Dermatologic symptoms associated with the multikinase inhibitor sorafenib. J Am Acad Dermatol. 2009;60(2):299–305.PubMedGoogle Scholar
  77. 77.
    Villalon G, Martin JM, Pinazo MI, Calduch L, Alonso V, Jorda E. Focal acral hyperpigmentation in a patient undergoing chemotherapy with capecitabine. Am J Clin Dermatol. 2009;10(4):261–3.PubMedGoogle Scholar
  78. 78.
    Lopez V, Molina I, Martin JM, Santonja N, Forner MJ, Jorda E. Eruptive nevi in a patient receiving cyclosporine A for psoriasis treatment. Arch Dermatol. 2010;146(7):802–4.PubMedGoogle Scholar
  79. 79.
    de Boer NK, Kuyvenhoven JP. Eruptive benign melanocytic naevi during immunosuppressive therapy in a Crohn’s disease patient. Inflamm Bowel Dis. 2011;17(6):E26.PubMedGoogle Scholar
  80. 80.
    Ibsen HH, Clemmensen O. Eruptive nevi in Addison’s disease. Arch Dermatol. 1990;126(9):1239–40.PubMedGoogle Scholar
  81. 81.
    Shoji T, Cockerell CJ, Koff AB, Bhawan J. Eruptive melanocytic nevi after Stevens-Johnson syndrome. J Am Acad Dermatol. 1997;37(2 Pt 2):337–9.PubMedGoogle Scholar
  82. 82.
    Berg D, Otley CC. Skin cancer in organ transplant recipients: epidemiology, pathogenesis, and management. J Am Acad Dermatol. 2002;47(1):1–17. quiz 8–20.PubMedGoogle Scholar
  83. 83.
    Hollenbeak CS, Todd MM, Billingsley EM, Harper G, Dyer AM, Lengerich EJ. Increased incidence of melanoma in renal transplantation recipients. Cancer. 2005;104(9):1962–7.PubMedGoogle Scholar
  84. 84.
    Le Mire L, Hollowood K, Gray D, Bordea C, Wojnarowska F. Melanomas in renal transplant recipients. Br J Dermatol. 2006;154(3):472–7.PubMedGoogle Scholar
  85. 85.
    Laing ME, Moloney FJ, Comber H, Conlon P, Murphy GM. Malignant melanoma in renal transplant recipients. Br J Dermatol. 2006;155(4):857.PubMedGoogle Scholar
  86. 86.
    Brewer JD, Christenson LJ, Weaver AL, Dapprich DC, Weenig RH, Lim KK, et al. Malignant melanoma in solid transplant recipients: collection of database cases and comparison with surveillance, epidemiology, and end results data for outcome analysis. Arch Dermatol. 2011;147(7):790–6.PubMedGoogle Scholar
  87. 87.
    Colegio OR, Billingsley EM. Skin cancer in transplant recipients. Out of the woods. Scientific retreat of the ITSCC and SCOPE. Am J Transplant. 2011;11(8):1584–91.PubMedGoogle Scholar
  88. 88.
    Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, et al. High frequency of BRAF mutations in nevi. Nat Genet. 2003;33(1):19–20.PubMedGoogle Scholar
  89. 89.
    Dong J, Phelps RG, Qiao R, Yao S, Benard O, Ronai Z, et al. BRAF oncogenic mutations correlate with progression rather than initiation of human melanoma. Cancer Res. 2003;63(14):3883–5.PubMedGoogle Scholar
  90. 90.
    Uribe P, Wistuba II, Gonzalez S. BRAF mutation: a frequent event in benign, atypical, and malignant melanocytic lesions of the skin. Am J Dermatopathol. 2003;25(5):365–70.PubMedGoogle Scholar
  91. 91.
    Kumar R, Angelini S, Snellman E, Hemminki K. BRAF mutations are common somatic events in melanocytic nevi. J Invest Dermatol. 2004;122(2):342–8.PubMedGoogle Scholar
  92. 92.
    Ichii-Nakato N, Takata M, Takayanagi S, Takashima S, Lin J, Murata H, et al. High frequency of BRAFV600E mutation in acquired nevi and small congenital nevi, but low frequency of mutation in medium-sized congenital nevi. J Invest Dermatol. 2006;126(9):2111–8.PubMedGoogle Scholar
  93. 93.
    Peyssonnaux C, Eychene A. The Raf/MEK/ERK pathway: new concepts of activation. Biol Cell. 2001;93(1–2):53–62.PubMedGoogle Scholar
  94. 94.
    Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949–54.PubMedGoogle Scholar
  95. 95.
    Zebisch A, Troppmair J. Back to the roots: the remarkable RAF oncogene story. Cell Mol Life Sci. 2006;63(11):1314–30.PubMedGoogle Scholar
  96. 96.
    Sekulic A, Colgan MB, Davis MD, DiCaudo DJ, Pittelkow MR. Activating BRAF mutations in eruptive melanocytic naevi. Br J Dermatol. 2010;163(5):1095–8.PubMedGoogle Scholar
  97. 97.
    Takata M, Murata H, Saida T. Molecular pathogenesis of malignant melanoma: a different perspective from the studies of melanocytic nevus and acral melanoma. Pigment Cell Melanoma Res. 2010;23(1):64–71.PubMedGoogle Scholar
  98. 98.
    Drobetsky EA, Turcotte J, Chateauneuf A. A role for ultraviolet A in solar mutagenesis. Proc Natl Acad Sci USA. 1995;92(6):2350–4.PubMedGoogle Scholar
  99. 99.
    Brash DE, Rudolph JA, Simon JA, Lin A, McKenna GJ, Baden HP, et al. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc Natl Acad Sci USA. 1991;88(22):10124–8.PubMedGoogle Scholar
  100. 100.
    Xing M. BRAF mutation in thyroid cancer. Endocr Relat Cancer. 2005;12(2):245–62.PubMedGoogle Scholar
  101. 101.
    Mathur A, Moses W, Rahbari R, Khanafshar E, Duh QY, Clark O. Higher rate of BRAF mutation in papillary thyroid cancer over time: a single-institution study. Cancer. 2011;117(19):4390–5.PubMedGoogle Scholar
  102. 102.
    Paik PK, Arcila ME, Fara M, Sima CS, Miller VA, Kris MG, et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol. 2011;29(15):2046–51.PubMedGoogle Scholar
  103. 103.
    Tol J, Nagtegaal ID, Punt CJ. BRAF mutation in metastatic colorectal cancer. N Engl J Med. 2009;361(1):98–9.PubMedGoogle Scholar
  104. 104.
    Maldonado JL, Fridlyand J, Patel H, Jain AN, Busam K, Kageshita T, et al. Determinants of BRAF mutations in primary melanomas. J Natl Cancer Inst. 2003;95(24):1878–90.PubMedGoogle Scholar
  105. 105.
    Jhappan C, Noonan FP, Merlino G. Ultraviolet radiation and cutaneous malignant melanoma. Oncogene. 2003;22(20):3099–112.PubMedGoogle Scholar
  106. 106.
    Gross S, Knebel A, Tenev T, Neininger A, Gaestel M, Herrlich P, et al. Inactivation of protein-tyrosine phosphatases as mechanism of UV-induced signal transduction. J Biol Chem. 1999;274(37):26378–86.PubMedGoogle Scholar
  107. 107.
    Rouzaud F, Kadekaro AL, Abdel-Malek ZA, Hearing VJ. MC1R and the response of melanocytes to ultraviolet radiation. Mutat Res. 2005;571(1–2):133–52.PubMedGoogle Scholar
  108. 108.
    Archambault M, Yaar M, Gilchrest BA. Keratinocytes and fibroblasts in a human skin equivalent model enhance melanocyte survival and melanin synthesis after ultraviolet irradiation. J Invest Dermatol. 1995;104(5):859–67.PubMedGoogle Scholar
  109. 109.
    Tada A, Suzuki I, Im S, Davis MB, Cornelius J, Babcock G, et al. Endothelin-1 is a paracrine growth factor that modulates melanogenesis of human melanocytes and participates in their responses to ultraviolet radiation. Cell Growth Differ. 1998;9(7):575–84.PubMedGoogle Scholar

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© Springer- Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Dermatology ServiceMemorial Sloan-Kettering Cancer CenterNew YorkUSA

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