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From Melanocytes to Melanoma pp 265–290Cite as

The Biology and Genetics of Melanoma

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Abstract

Like all human malignancies, the incidence of melanoma reflects the interaction of genetic predisposition with environmental exposures. Melanoma is perhaps unusual in this regard, however, in that in no other common tumor type is there such an advanced understanding of both the underlying environmental and genetic factors. The majority of melanoma occurs in the setting of a common environmental exposure: ultraviolet irradiation. Likewise, several congenital melanoma-prone genetic conditions have been identified, including germline polymorphisms that attenuate cell cycle regulation, that decrease skin pigmentation, that hamper DNA repair, and that impair melanocytic differentiation. Lastly, the large majority of sporadic melanomas share 2 classes of acquired mutations: those affecting RAS-RAF signaling and those that target the INK4a/ARF locus on chromosome 9p21. This well-developed comprehension of both the environmental and genetic causes of this disease has allowed for the generation of sophisticated in vitro and murine models, which have reinforced and furthered our understanding of the development of this cancer. This chapter reviews decades’ worth of genetic and biologic insights from the study of these models, and their contribution to our understanding of the pathogenesis of melanoma. A review of this work also makes obvious the continued challenges in the field: to use our hard-earned molecular comprehension of this disease to elucidate the disturbing clinical features of melanoma; namely, an intense therapeutic resistance and proclivity for early metastasis. The present ability to study faithful murine melanoma models, coupled with advances in rational drug design, has generated optimism for the development of effective prevention and screening programs, as well as successful targeted therapeutics in the near future.

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Authors and Affiliations

  1. Department of Medicine and Genetics, The University of North Carolina School of Medicine, Chapel Hill, NC

    Norman E. Sharpless

  2. Department of Medical Oncology, Dana-Farber Cancer Institute, and the Department of Dermatology, Harvard Medical School, Boston, MA

    Lynda Chin

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  1. Norman E. Sharpless
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  1. Laboratory of Cell Biology National Cancer Institute, National Institutes of Health, Bethesda, MD

    Vincent J. Hearing PhD

  2. Department of Surgery, University of California, San Francisco

    Stanley P. L. Leong MD

  3. School of Medicine, San Francisco, CA

    Stanley P. L. Leong MD

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Sharpless, N.E., Chin, L. (2006). The Biology and Genetics of Melanoma. In: Hearing, V.J., Leong, S.P.L. (eds) From Melanocytes to Melanoma. Humana Press. https://doi.org/10.1007/978-1-59259-994-3_15

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