Advertisement

Nevogenesis pp 137-144 | Cite as

Malignant Transformation of Melanocytic Nevi

  • Alexander Marzuka-Alcalá
  • Hensin TsaoEmail author
Chapter
  • 462 Downloads

Abstract

Most cutaneous melanomas are thought to arise de novo from resident melanocytes in the skin. The nevus as a precursor lesion of melanoma has been a long-held clinical tenet, although there has been much debate on the molecular nature of nevi and its relationship to melanoma. The purpose of this chapter is to show evidence that nevi share common etiologic origins as melanoma and may therefore undergo the clinical observation of malignant transformation.

Keywords

BRAF Mutation Cutaneous Melanoma Uveal Melanoma BRAF V600E Mutation Melanocytic Nevus 
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.

References

  1. 1.
    Gill M, Celebi JT. B-RAF and melanocytic neoplasia. J Am Acad Dermatol. 2005;53:108–14.PubMedCrossRefGoogle Scholar
  2. 2.
    Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417: 949–54.PubMedCrossRefGoogle Scholar
  3. 3.
    Hocker T, Tsao H. Ultraviolet radiation and melanoma: a systematic review and analysis of reported sequence variants. Hum Mutat. 2007;28:578–88.PubMedCrossRefGoogle Scholar
  4. 4.
    Kumar R, Angelini S, Snellman E, Hemminki K. BRAF mutations are common somatic events in melanocytic nevi. J Invest Dermatol. 2004;122:342–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Pollock PM, Harper UL, Hansen KS, et al. High frequency of BRAF mutations in nevi. Nat Genet. 2003;33:19–20.PubMedCrossRefGoogle Scholar
  6. 6.
    Loewe R, Kittler H, Fischer G, Fae I, Wolff K, Petzelbauer P. BRAF kinase gene V599E mutation in growing melanocytic lesions. J Invest Dermatol. 2004;123:733–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Qi RH, He L, Zheng S, et al. BRAF Exon 15 T1799A mutation is common in melanocytic nevi, but less prevalent in cutaneous malignant melanoma, in Chinese Han [published online ahead of print February 17, 2011]. J Invest Dermatol.  doi:10.1038/jid.2010.405.
  8. 8.
    Carr J, Mackie RM. Point mutations in the N-ras oncogene in malignant melanoma and congenital nevi. Br J Dermatol. 1994;131:72–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Herlyn M, Satyamoorthy K. Activated ras. Yet another player in melanoma. Am J Pathol. 1996;149:739–44.PubMedGoogle Scholar
  10. 10.
    Reifenberger J, Knobbe CB, Sterzinger AA, et al. Frequent alterations of Ras signaling pathway genes in sporadic malignant melanomas. Int J Cancer. 2004;109:377–84.PubMedCrossRefGoogle Scholar
  11. 11.
    Poynter JN, Elder JT, Fullen DR, et al. BRAF and NRAS mutations in melanoma and melanocytic nevi. Melanoma Res. 2006;16:267–73.PubMedCrossRefGoogle Scholar
  12. 12.
    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. 1998;111:757–61.PubMedCrossRefGoogle Scholar
  13. 13.
    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. 1996;149:883–93.PubMedGoogle Scholar
  14. 14.
    Demunter A, Stas M, Degreef H, De Wolf-Peeters C, van den Oord JJ. Analysis of N- and K-ras mutations in the distinctive tumor progression phases of melanoma. J Invest Dermatol. 2001;117:1483–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Phadke PA, Rakheja D, Le LP, et al. Proliferative nodules arising within congenital nevi: a histological, immunohistochemical, and molecular analyses of 43 cases [published online ahead of print March 22, 2011]. Am J Surg Pathol. doi: 10.1097/PAS.0b013e31821433af.
  16. 16.
    Wu D, Wang M, Wang X, et al. Lack of BRAFV600E mutations in giant congenital melanocytic nevi in a Chinese population [published online ahead of print March 11, 2011]. Am J Dermatopathol. doi: 10.1097/DAD.0b013e3181fb5bc7.
  17. 17.
    Bauer J, Curtin JA, Pinkel D, Bastian BC. Congenital melanocytic nevi frequently harbor NRAS mutations but no BRAF mutations. J Invest Dermatol. 2007;127:179–82.PubMedCrossRefGoogle Scholar
  18. 18.
    Singh AD, De Potter P, Fijal BA, Shields CL, Shields JA, Elston RC. Lifetime prevalence of uveal melanoma in white patients with oculo(dermal) melanocytosis. Ophthalmology. 1998;105:195–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Van Raamsdonk CD, Bezrookove V, Green G, et al. Frequent somatic mutations of GNAQ in uveal melanoma and blue nevi. Nature. 2009;457:599–602.PubMedCrossRefGoogle Scholar
  20. 20.
    Serrano M, Blasco MA. Putting the stress on senescence. Curr Opin Cell Biol. 2001;13:748–53.PubMedCrossRefGoogle Scholar
  21. 21.
    Collado M, Serrano M. The power and the promise of oncogene-induced senescence markers. Nat Rev Cancer. 2006;6:472–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbours. Cell. 2005;120:512–22.CrossRefGoogle Scholar
  23. 23.
    Hollstein M, Sidransky D, Vogelstein B, Harris C. p53 mutations in human cancers. Science. 1991;253:49–53.PubMedCrossRefGoogle Scholar
  24. 24.
    Ruas M, Peters G. The p16INK4a/CDKN2A tumor suppressor and its relatives. Biochem Biophys Acta. 1998;1378:F115–77.PubMedGoogle Scholar
  25. 25.
    Sharpless NE, DePinho RA. The INK4A/ARF locus and its two gene products. Curr Opin Genet Dev. 1999;9:22–30.PubMedCrossRefGoogle Scholar
  26. 26.
    Michaloglou C, Vredeveld LCW, Soengas MS. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature. 2005;436(7051):720–4.PubMedCrossRefGoogle Scholar
  27. 27.
    Gray-Schopfer VC, Cheong SC, Chong H, et al. Cellular senescence in naevi and immortalisation in melanoma: a role for p16? Br J Cancer. 2006;95:496–505.PubMedCrossRefGoogle Scholar
  28. 28.
    Huot TJ, Rowe J, Harland M, et al. Biallelic mutations in p16INK4a confer resistance to Ras- and Ets-induced senescence in human diploid fibroblasts. Mol Cell Biol. 2002;22:8135–43.PubMedCrossRefGoogle Scholar
  29. 29.
    Dhomen N, Reis-Filho JS, da Rocha Dias S. Oncogenic Braf induces melanocyte senescence and melanoma in mice. Cancer Cell. 2009;15:294–303.PubMedCrossRefGoogle Scholar
  30. 30.
    Tsao H, Bevona C, Goggins W, Quinn T. The transformation rate of moles (melanocytic nevi) into cutaneous melanoma. Arch Dermatol. 2003;139:282–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Bevona C, Goggins W, Quinn T, Fullerton J, Tsao H. Cutaneous melanomas associated with nevi. Arch Dermatol. 2003;139:1620–4.PubMedCrossRefGoogle Scholar

Copyright information

© Springer- Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Yale DermatopathologyYale School of MedicineNew HavenUSA
  2. 2.Wellman Center for Photomedicine, Department of Dermatology and MGH Cancer CenterMassachusetts General HospitalBostonUSA

Personalised recommendations