Sun-induced freckling: Ephelides and solar lentigines

Pigment Cell and Melanoma Research

Volumn 27, Issue 3, 2014, Pages 339-350

  Praetorius, Christian ^a   Sturm, Richard A ^b   Steingrimsson, Eirikur ^a  

^a UNIVERSITY OF ICELAND   (Iceland)

^b UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

Ephelides; Freckles; Melanocytes; Solar lentigines; Stem cells

Indexed keywords

AFAMELANOTIDE; DOPA; INTERFERON REGULATORY FACTOR 4; MELANIN; PHEOMELANIN; PSORALEN DERIVATIVE; AGOUTI PROTEIN; ASIP PROTEIN, HUMAN; MELANOCORTIN 1 RECEPTOR; MONOPHENOL MONOOXYGENASE;

ARTICLE; CARNEY COMPLEX; CELL AGING; CELL PROLIFERATION; EPHELIDES; EPIDEMIOLOGICAL DATA; EPIGENETICS; GENE EXPRESSION; GENETIC ANALYSIS; HAIR FOLLICLE; HISTOPATHOLOGY; HUMAN; IMMUNOHISTOCHEMISTRY; KERATINOCYTE; LENTIGO; LEOPARD SYNDROME; MELANOCYTE; MELANOMA SKIN CANCER; MELANOSOME; NEVUS; PEUTZ JEGHERS SYNDROME; PIGMENT DISORDER; PSORIASIS; PUVA; RISK FACTOR; SCREENING TEST; SINGLE NUCLEOTIDE POLYMORPHISM; SKIN CANCER; SKIN COLOR; SKIN PIGMENTATION; SOLAR LENTIGINES; SOLAR RADIATION; SUN EXPOSURE; SUNBURN; SUNLIGHT; VITILIGO; ANIMAL; BIOLOGICAL MODEL; BIOSYNTHESIS; ETHNIC GROUP; GENE EXPRESSION REGULATION; GENETICS; HAIR COLOR; MELANOSIS; METABOLISM; ONSET AGE; PATHOLOGY; PHOTOSENSITIVITY DISORDERS; PHYSIOLOGY; RADIATION RESPONSE; SYNDROME; ULTRASTRUCTURE;

AGE OF ONSET; AGOUTI SIGNALING PROTEIN; ANIMALS; ETHNIC GROUPS; GENE EXPRESSION REGULATION; HAIR COLOR; HUMANS; KERATINOCYTES; LENTIGO; MELANINS; MELANOCYTES; MELANOSIS; MELANOSOMES; MODELS, BIOLOGICAL; MONOPHENOL MONOOXYGENASE; PHOTOSENSITIVITY DISORDERS; RECEPTOR, MELANOCORTIN, TYPE 1; SKIN PIGMENTATION; SUNLIGHT; SYNDROME;

EID: 84898894375     PISSN: 17551471     EISSN: 1755148X     Source Type: Journal    
DOI: 10.1111/pcmr.12232     Document Type: Article

References (114)

1. Abel, E.A., Reid, H., Wood, C., and Hu, C.-H. (1985). PUVA-induced melanocytic atypia: is it confined to PUVA lentigines? J. Am. Acad. Dermatol. 13, 761-768.
2. Adameyko, I., Lallemend, F., Aquino, J.B. et al. (2009). Schwann cell precursors from nerve innervation are a cellular origin of melanocytes in skin. Cell 139, 366-379.
3. Andersen, W.K., Labadie, R.R., and Bhawan, J. (1997). Histopathology of solar lentigines of the face: a quantitative study. J. Am. Acad. Dermatol. 36, 444-447.
4. Bastiaens, M.T., Westendorp, R.G., Vermeer, B.J., and Bavinck, J.N. (1999). Ephelides are more related to pigmentary constitutional host factors than solar lentigines. Pigment Cell Res. 12, 316-322.
5. Bastiaens, M., Ter Huurne, J., Gruis, N., Bergman, W., Westendorp, R., Vermeer, B.J., and Bouwes Bavinck, J.N. (2001). The melanocortin-1-receptor gene is the major freckle gene. Hum. Mol. Genet. 10, 1701-1708.
6. Bastiaens, M., Hoefnagel, J., Westendorp, R., Vermeer, B.J., and Bouwes Bavinck, J.N. (2004). Solar lentigines are strongly related to sun exposure in contrast to ephelides. Pigment Cell Res. 17, 225-229.
7. Bataille, V., Snieder, H., Macgregor, A.J., Sasieni, P., and Spector, T.D. (2000). Genetics of risk factors for melanoma: an adult twin study of nevi and freckles. J. Natl Cancer Inst. 92, 457-463.
8. Beaumont, K.A., Shekar, S.N., Newton, R.A., James, M.R., Stow, J.L., Duffy, D.L., and Sturm, R.A. (2007). Receptor function, dominant negative activity and phenotype correlations for MC1R variant alleles. Hum. Mol. Genet. 16, 2249-2260.
9. Beaumont, K.A., Shekar, S.N., Cook, A.L., Duffy, D.L., and Sturm, R.A. (2008). Red hair is the null phenotype of MC1R. Hum. Mutat. 29, E88-E94.
10. Beaumont, K.A., Liu, Y.Y., and Sturm, R.A. (2009). The melanocortin-1 receptor gene polymorphism and association with human skin cancer. Prog. Mol. Biol. Transl. Sci. 88, 85-153.
11. Beaumont, K.A., Wong, S.S., Ainger, S.A. et al. (2011). Melanocortin MC(1) receptor in human genetics and model systems. Eur. J. Pharmacol. 660, 103-110.
12. Bliss, J.M., Ford, D., Swerdlow, A.J. et al. (1995). Risk of cutaneous melanoma associated with pigmentation characteristics and freckling: systematic overview of 10 case-control studies. The International Melanoma Analysis Group (IMAGE). Int. J. Cancer 62, 367-376.
13. Box, N.F., Wyeth, J.R., O'gorman, L.E., Martin, N.G., and Sturm, R.A. (1997). Characterization of melanocyte stimulating hormone receptor variant alleles in twins with red hair. Hum. Mol. Genet. 6, 1891-1897.
14. Breathnach, A.S. (1957). Melanocyte distribution in forearm epidermis of freckled human subjects. J. Invest. Dermatol. 29, 253-261.
15. Breathnach, A.S. (1958). Observations on tyrosinase activity in melanocytes of freckled human epidermis. J. Invest. Dermatol. 30, 153-158.
16. Breathnach, A.S., and Wyllie, L.M. (1964). Electron microscopy of melanocytes and melanosomes in freckled human epidermis. J. Invest. Dermatol. 42, 389-394.
17. Busca, R., and Ballotti, R. (2000). Cyclic AMP a key messenger in the regulation of skin pigmentation. Pigment Cell Res. 13, 60-69.
18. Cario-Andre, M., Lepreux, S., Pain, C., Nizard, C., Noblesse, E., and Taieb, A. (2004). Perilesional vs. lesional skin changes in senile lentigo. J. Cutan. Pathol. 31, 441-447.
19. Chen, N., Hu, Y., Li, W.H., Eisinger, M., Seiberg, M., and Lin, C.B. (2010). The role of keratinocyte growth factor in melanogenesis: a possible mechanism for the initiation of solar lentigines. Exp. Dermatol. 19, 865-872.
20. Chhajlani, V., and Wikberg, J.E. (1992). Molecular cloning and expression of the human melanocyte stimulating hormone receptor cDNA. FEBS Lett. 309, 417-420.
21. Chou, W.C., Takeo, M., Rabbani, P., Hu, H., Lee, W., Chung, Y.R., Carucci, J., Overbeek, P., and Ito, M. (2013). Direct migration of follicular melanocyte stem cells to the epidermis after wounding or UVB irradiation is dependent on Mc1r signaling. Nat. Med. 19, 924-929.
22. Cone, R.D., Lu, D., Koppula, S. et al. (1996). The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation. Recent Prog. Horm. Res. 51, 287-317; discussion 318.
23. Cramer, S.F. (2009). Stem cells for epidermal melanocytes-a challenge for students of dermatopathology. Am. J. Dermatopathol. 31, 331-341.
24. Cui, R., Widlund, H.R., Feige, E. et al. (2007). Central role of p53 in the suntan response and pathologic hyperpigmentation. Cell 128, 853-864.
25. Dellavalle, R.P., Johnson, K.R., Hester, E.J., Deas, A.M., Mokrohisky, S., Morelli, J.G., and Crane, L.A. (2005). Children with red hair have more freckles but fewer melanocytic nevi: results from a cohort study of 280 three-year-olds. Arch. Dermatol. 141, 1042-1043.
26. Derancourt, C., Bourdon-Lanoy, E., Grob, J.J., Guillaume, J.C., Bernard, P., and Bastuji-Garin, S. (2007). Multiple large solar lentigos on the upper back as clinical markers of past severe sunburn: a case-control study. Dermatology 214, 25-31.
27. Digilio, M.C., Sarkozy, A., De Zorzi, A., Pacileo, G., Limongelli, G., Mingarelli, R., Calabro, R., Marino, B., and Dallapiccola, B. (2006). LEOPARD syndrome: clinical diagnosis in the first year of life. Am. J. Med. Genet. A 140, 740-746.
28. Dubin, N., Pasternack, B.S., and Moseson, M. (1990). Simultaneous assessment of risk factors for malignant melanoma and non-melanoma skin lesions, with emphasis on sun exposure and related variables. Int. J. Epidemiol. 19, 811-819.
29. Duffy, D.L., Box, N.F., Chen, W., Palmer, J.S., Montgomery, G.W., James, M.R., Hayward, N.K., Martin, N.G., and Sturm, R.A. (2004). Interactive effects of MC1R and OCA2 on melanoma risk phenotypes. Hum. Mol. Genet. 13, 447-461.
30. Duffy, D.L., Iles, M.M., Glass, D. et al. (2010a). IRF4 variants have age-specific effects on nevus count and predispose to melanoma. Am. J. Hum. Genet. 87, 6-16.
31. Duffy, D.L., Zhao, Z.Z., Sturm, R.A., Hayward, N.K., Martin, N.G., and Montgomery, G.W. (2010b). Multiple pigmentation gene polymorphisms account for a substantial proportion of risk of cutaneous malignant melanoma. J. Invest. Dermatol. 130, 520-528.
32. Eriksson, N., Macpherson, J.M., Tung, J.Y. et al. (2010). Web-based, participant-driven studies yield novel genetic associations for common traits. PLoS Genet. 6, e1000993.
33. Espiard, S., and Bertherat, J. (2013). Carney complex. Front. Horm. Res. 41, 50-62.
34. Ezzedine, K., Mauger, E., Latreille, J. et al. (2013). Freckles and solar lentigines have different risk factors in Caucasian women. J. Eur. Acad. Dermatol. Venereol. 27, e345-e356.
35. Flanagan, N., Healy, E., Ray, A., Philips, S., Todd, C., Jackson, I.J., Birch-Machin, M.A., and Rees, J.L. (2000). Pleiotropic effects of the melanocortin 1 receptor (MC1R) gene on human pigmentation. Hum. Mol. Genet. 9, 2531-2537.
36. Frudakis, T., Thomas, M., Gaskin, Z. et al. (2003). Sequences associated with human iris pigmentation. Genetics 165, 2071-2083.
37. Garbe, C., Buttner, P., Weiss, J. et al. (1994). Associated factors in the prevalence of more than 50 common melanocytic nevi, atypical melanocytic nevi, and actinic lentigines: multicenter case-control study of the Central Malignant Melanoma Registry of the German Dermatological Society. J. Invest. Dermatol. 102, 700-705.
38. Garcia-Borron, J.C., Sanchez-Laorden, B.L., and Jimenez-Cervantes, C. (2005). Melanocortin-1 receptor structure and functional regulation. Pigment Cell Res. 18, 393-410.
39. Gerstenblith, M.R., Goldstein, A.M., Fargnoli, M.C., Peris, K., and Landi, M.T. (2007). Comprehensive evaluation of allele frequency differences of MC1R variants across populations. Hum. Mutat. 28, 495-505.
40. Gordon, P.R., Mansur, C.P., and Gilchrest, B.A. (1989). Regulation of human melanocyte growth, dendricity, and melanization by keratinocyte derived factors. J. Invest. Dermatol. 92, 565-572.
41. Goyarts, E., Muizzuddin, N., Maes, D., and Giacomoni, P.U. (2007). Morphological changes associated with aging: age spots and the microinflammatory model of skin aging. Ann. N.Y. Acad. Sci. 1119, 32-39.
42. Grichnik, J.M. (2008). Melanoma, nevogenesis, and stem cell biology. J. Invest. Dermatol. 128, 2365-2380.
43. Grimes, P.E., Hamzavi, I., Lebwohl, M., Ortonne, J.P., and Lim, H.W. (2013). The efficacy of afamelanotide and narrowband UV-B phototherapy for repigmentation of vitiligo. JAMA Dermatol. 149, 68-73.
44. Hafner, C., Stoehr, R., Van Oers, J.M., Zwarthoff, E.C., Hofstaedter, F., Landthaler, M., Hartmann, A., and Vogt, T. (2009). FGFR3 and PIK3CA mutations are involved in the molecular pathogenesis of solar lentigo. Br. J. Dermatol. 160, 546-551.
45. Han, J., Kraft, P., Nan, H. et al. (2008). A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation. PLoS Genet. 4, e1000074.
46. Hattori, H., Kawashima, M., Ichikawa, Y., and Imokawa, G. (2004). The epidermal stem cell factor is over-expressed in lentigo senilis: implication for the mechanism of hyperpigmentation. J. Invest. Dermatol. 122, 1256-1265.
47. Hemminki, A., Markie, D., Tomlinson, I. et al. (1998). A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 391, 184-187.
48. Herlyn, M., Berking, C., Li, G., and Satyamoorthy, K. (2000). Lessons from melanocyte development for understanding the biological events in naevus and melanoma formation. Melanoma Res. 10, 303-312.
49. Hirobe, T. (1992). Control of melanocyte proliferation and differentiation in the mouse epidermis. Pigment Cell Res. 5, 1-11.
50. Hirobe, T. (2005). Role of keratinocyte-derived factors involved in regulating the proliferation and differentiation of mammalian epidermal melanocytes. Pigment Cell Res. 18, 2-12.
51. Hodgson, C. (1963). Senile lentigo. Arch. Dermatol. 87, 197-207.
52. Horvath, A., and Stratakis, C.A. (2009). Carney complex and lentiginosis. Pigment Cell Melanoma Res. 22, 580-587.
53. Hsu, M.-Y., Meier, F., and Herlyn, M. (2002). Melanoma development and progression: a conspiracy between tumor and host. Differentiation 70, 522-536.
54. Iuchi, S., and Green, H. (1999). Basonuclin, a zinc finger protein of keratinocytes and reproductive germ cells, binds to the rRNA gene promoter. Proc. Natl Acad. Sci. U.S.A. 96, 9628-9632.
55. Jacobs, L.C., Wollstein, A., Lao, O., Hofman, A., Klaver, C.C., Uitterlinden, A.G., Nijsten, T., Kayser, M., and Liu, F. (2013). Comprehensive candidate gene study highlights UGT1A and BNC2 as new genes determining continuous skin color variation in Europeans. Hum. Genet. 132, 147-158.
56. Jang, K.A., Chung, E.C., Choi, J.H., Sung, K.J., Moon, K.C., and Koh, J.K. (2000). Successful removal of freckles in Asian skin with a Q-switched alexandrite laser. Dermatol. Surg. 26, 231-234.
57. Jimbow, K., Quevedo, W.C. Jr, Fitzpatrick, T.B., and Szabo, G. (1976). Some aspects of melanin biology: 1950-1975. J. Invest. Dermatol. 67, 72-89.
58. Kadono, S., Manaka, I., Kawashima, M., Kobayashi, T., and Imokawa, G. (2001). The role of the epidermal endothelin cascade in the hyperpigmentation mechanism of lentigo senilis. J. Invest. Dermatol. 116, 571-577.
59. Kawa, Y., Ito, M., Ono, H. et al. (2000). Stem cell factor and/or endothelin-3 dependent immortal melanoblast and melanocyte populations derived from mouse neural crest cells. Pigment Cell Res. 13(Suppl 8), 73-80.
60. Kijas, J.M., Wales, R., Tornsten, A., Chardon, P., Moller, M., and Andersson, L. (1998). Melanocortin receptor 1 (MC1R) mutations and coat color in pigs. Genetics 150, 1177-1185.
61. Kirschner, L.S., Carney, J.A., Pack, S.D., Taymans, S.E., Giatzakis, C., Cho, Y.S., Cho-Chung, Y.S., and Stratakis, C.A. (2000). Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. Nat. Genet. 26, 89-92.
62. Kovacs, D., Cardinali, G., Aspite, N. et al. (2010). Role of fibroblast-derived growth factors in regulating hyperpigmentation of solar lentigo. Br. J. Dermatol. 163, 1020-1027.
63. Lang, M.R., Patterson, L.B., Gordon, T.N., Johnson, S.L., and Parichy, D.M. (2009). Basonuclin-2 requirements for zebrafish adult pigment pattern development and female fertility. PLoS Genet. 5, e1000744.
64. Lauriol, J., and Kontaridis, M.I. (2011). PTPN11-associated mutations in the heart: has LEOPARD changed Its RASpots? Trends Cardiovasc. Med. 21, 97-104.
65. Li, L., Fukunaga-Kalabis, M., Yu, H., Xu, X., Kong, J., Lee, J.T., and Herlyn, M. (2010). Human dermal stem cells differentiate into functional epidermal melanocytes. J. Cell Sci. 123, 853-860.
66. Mackie, R.M. (1998). Incidence, risk factors and prevention of melanoma. Eur. J. Cancer 34(Suppl 3), S3-S6.
67. Makova, K., and Norton, H. (2005). Worldwide polymorphism at the MC1R locus and normal pigmentation variation in humans. Peptides 26, 1901-1908.
68. Monestier, S., Gaudy, C., Gouvernet, J., Richard, M.A., and Grob, J.J. (2006). Multiple senile lentigos of the face, a skin ageing pattern resulting from a life excess of intermittent sun exposure in dark-skinned caucasians: a case-control study. Br. J. Dermatol. 154, 438-444.
69. Montagna, W., Hu, F., and Carlisle, K. (1980). A reinvestigation of solar lentigines. Arch. Dermatol. 116, 1151-1154.
70. Motokawa, T., Kato, T., Hashimoto, Y., and Katagiri, T. (2007). Effect of Val92Met and Arg163Gln variants of the MC1R gene on freckles and solar lentigines in Japanese. Pigment Cell Res. 20, 140-143.
71. Motokawa, T., Kato, T., Hashimoto, Y., Takimoto, H., Yamamoto, H., and Katagiri, T. (2008). Polymorphism patterns in the promoter region of the MC1R gene are associated with development of freckles and solar lentigines. J. Invest. Dermatol. 128, 1588-1591.
72. Mountjoy, K.G., Robbins, L.S., Mortrud, M.T., and Cone, R.D. (1992). The cloning of a family of genes that encode the melanocortin receptors. Science 257, 1248-1251.
73. Nakagawa, H., Rhodes, A.R., Momtaz, T.K., and Fitzpatrick, T.B. (1984). Morphologic alterations of epidermal melanocytes and melanosomes in PUVA lentigines: a comparative ultrastructural investigation of lentigines induced by PUVA and sunlight. J. Invest. Dermatol. 82, 101-107.
74. Neel, B.G., Gu, H., and Pao, L. (2003). The 'Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem. Sci. 28, 284-293.
75. Nicholls, E.M. (1968). Genetic susceptibility and somatic mutation in the production of freckles, birthmarks and moles. Lancet 1, 71-73.
76. Nishimura, E.K., Jordan, S.A., Oshima, H. et al. (2002). Dominant role of the niche in melanocyte stem-cell fate determination. Nature 416, 854-860.
77. Noblesse, E., Nizard, C., Cario-Andre, M., Lepreux, S., Pain, C., Schnebert, S., Taieb, A., and Kurfurst, R. (2006). Skin ultrastructure in senile lentigo. Skin Pharmacol. Physiol. 19, 95-100.
78. Ollila, S., and Makela, T.P. (2011). The tumor suppressor kinase LKB1: lessons from mouse models. J. Mol. Cell Biol. 3, 330-340.
79. Patterson, L.B., and Parichy, D.M. (2013). Interactions with iridophores and the tissue environment required for patterning melanophores and xanthophores during zebrafish adult pigment stripe formation. PLoS Genet. 9, e1003561.
80. Plensdorf, S., and Martinez, J. (2009). Common pigmentation disorders. Am. Fam. Physician 79, 109-116.
81. Praetorius, C., Grill, C., Stacey, SN et al. (2013). A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway. Cell 155, 1022-1033.
82. Rees, J.L. (2003). Genetics of hair and skin color. Annu. Rev. Genet. 37, 67-90.
83. Rees, J. (2004). Genes for freckles. J. Invest. Dermatol. 123, 414.
84. Rhodes, A.R., Stern, R.S., and Melski, J.W. (1983). The PUVA lentigo: an analysis of predisposing factors. J. Invest. Dermatol. 81, 459-463.
85. Rhodes, A.R., Albert, L.S., Barnhill, R.L., and Weinstock, M.A. (1991). Sun-induced freckles in children and young adults. A correlation of clinical and histopathologic features. Cancer 67, 1990-2001.
86. Robbins, L.S., Nadeau, J.H., Johnson, K.R., Kelly, M.A., Roselli-Rehfuss, L., Baack, E., Mountjoy, K.G., and Cone, R.D. (1993). Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function. Cell 72, 827-834.
87. Romano, R.A., Li, H., Tummala, R., Maul, R., and Sinha, S. (2004). Identification of Basonuclin2, a DNA-binding zinc-finger protein expressed in germ tissues and skin keratinocytes. Genomics 83, 821-833.
88. Rouzaud, F., Costin, G.E., Yamaguchi, Y. et al. (2006). Regulation of constitutive and UVR-induced skin pigmentation by melanocortin 1 receptor isoforms. FASEB J. 20, 1927-1929.
89. Sassone-Corsi, P. (1998). Coupling gene expression to cAMP signalling: role of CREB and CREM. Int. J. Biochem. Cell Biol. 30, 27-38.
90. Shriver, M.D., Parra, E.J., Dios, S. et al. (2003). Skin pigmentation, biogeographical ancestry and admixture mapping. Hum. Genet. 112, 387-399.
91. Smith, R., Healy, E., Siddiqui, S. et al. (1998). Melanocortin 1 receptor variants in an Irish population. J. Invest. Dermatol. 111, 119-122.
92. Spigelman, A.D., Thomson, J.P., and Phillips, R.K. (1990). Towards decreasing the relaparotomy rate in the Peutz-Jeghers syndrome: the role of peroperative small bowel endoscopy. Br. J. Surg. 77, 301-302.
93. Sturm, R.A. (2009). Molecular genetics of human pigmentation diversity. Hum. Mol. Genet. 18, R9-R17.
94. Sulem, P., Gudbjartsson, D.F., Stacey, S.N. et al. (2007). Genetic determinants of hair, eye and skin pigmentation in Europeans. Nat. Genet. 39, 1443-1452.
95. Sulem, P., Gudbjartsson, D.F., Stacey, S.N. et al. (2008). Two newly identified genetic determinants of pigmentation in Europeans. Nat. Genet. 40, 835-837.
96. Sviderskaya, E.V., Wakeling, W.F., and Bennett, D.C. (1995). A cloned, immortal line of murine melanoblasts inducible to differentiate to melanocytes. Development 121, 1547-1557.
97. Tartaglia, M., Niemeyer, C.M., Shannon, K.M., and Loh, M.L. (2004). SHP-2 and myeloid malignancies. Curr. Opin. Hematol. 11, 44-50.
98. Tharmarajah, G., Faas, L., Reiss, K., Saftig, P., Young, A., and Van Raamsdonk, C.D. (2012). Adam10 haploinsufficiency causes freckle-like macules in Hairless mice. Pigment Cell Melanoma Res. 25, 555-565.
99. Titus-Ernstoff, L., Perry, A.E., Spencer, S.K., Gibson, J.J., Cole, B.F., and Ernstoff, M.S. (2005). Pigmentary characteristics and moles in relation to melanoma risk. Int. J. Cancer 116, 144-149.
100. Unver, N., Freyschmidt-Paul, P., Horster, S., Wenck, H., Stab, F., Blatt, T., and Elsasser, H.P. (2006). Alterations in the epidermal-dermal melanin axis and factor XIIIa melanophages in senile lentigo and ageing skin. Br. J. Dermatol. 155, 119-128.
101. Vage, D.I., Klungland, H., Lu, D., and Cone, R.D. (1999). Molecular and pharmacological characterization of dominant black coat color in sheep. Mamm. Genome 10, 39-43.
102. Valverde, P., Healy, E., Jackson, I., Rees, J.L., and Thody, A.J. (1995). Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans. Nat. Genet. 11, 328-330.
103. Vanhoutteghem, A., and Djian, P. (2004). Basonuclin 2: an extremely conserved homolog of the zinc finger protein basonuclin. Proc. Natl Acad. Sci. U.S.A. 101, 3468-3473.
104. Vanhoutteghem, A., and Djian, P. (2006). Basonuclins 1 and 2, whose genes share a common origin, are proteins with widely different properties and functions. Proc. Natl Acad. Sci. U.S.A. 103, 12423-12428.
105. Vanhoutteghem, A., and Djian, P. (2007). The human basonuclin 2 gene has the potential to generate nearly 90, 000 mRNA isoforms encoding over 2000 different proteins. Genomics 89, 44-58.
106. Vanhoutteghem, A., Maciejewski-Duval, A., Bouche, C. et al. (2009). Basonuclin 2 has a function in the multiplication of embryonic craniofacial mesenchymal cells and is orthologous to disco proteins. Proc. Natl Acad. Sci. U.S.A. 106, 14432-14437.
107. Vierkotter, A., Kramer, U., Sugiri, D., Morita, A., Yamamoto, A., Kaneko, N., Matsui, M., and Krutmann, J. (2012). Development of Lentigines in German and Japanese Women Correlates with Variants in the SLC45A2 Gene. J. Invest. Dermatol. 132, 733-736.
108. Wang, T., and Herlyn, M. (2013). The macrophage: a new factor in UVR-induced melanomagenesis. J. Invest. Dermatol. 133, 1711-1713.
109. Wang, J., Zhang, S., Schultz, R.M., and Tseng, H. (2006). Search for basonuclin target genes. Biochem. Biophys. Res. Commun. 348, 1261-1271.
110. Wilson, P.D., and Kligman, A.M. (1982). Experimental induction of freckles by ultraviolet-B. Br. J. Dermatol. 106, 401-406.
111. Yamada, T., Hasegawa, S., Inoue, Y. et al. (2014). Comprehensive analysis of melanogenesis and proliferation potential of melanocyte lineage in solar lentigines. J. Dermatol. Sci. 73, 251-257.
112. Yamaguchi, K., Watanabe, C., Kawaguchi, A. et al. (2012). Association of melanocortin 1 receptor gene (MC1R) polymorphisms with skin reflectance and freckles in Japanese. J. Hum. Genet. 57, 700-708.
113. Zeron-Medina, J., Wang, X., Repapi, E. et al. (2013). A polymorphic p53 response element in KIT ligand influences cancer risk and has undergone natural selection. Cell 155, 410-422.
114. Zhang, X.J., He, P.P., Liang, Y.H., Yang, S., Yuan, W.T., Xu, S.J., and Huang, W. (2004). A gene for freckles maps to chromosome 4q32-q34. J. Invest. Dermatol. 122, 286-290.