Abstract
The pathogenesis of melanoma depends on the occurrence of specific genetic changes that drive the neoplastic process. Much research has therefore focused on elucidating these changes with twin goals of comprehending the genetic basis of how a melanocyte becomes a melanoma and identifying vulnerabilities ripe for clinical intervention. One of the defining features of the melanoma genome is an extraordinarily high prevalence of C > T point mutations; in this regard, ultraviolet light represents the predominant force shaping the melanocyte genome. Several subtypes of melanoma and melanocytic neoplasms exist, each of which may harbor specific genetic changes. Recent genetic and genomic studies have revealed an overarching framework for the mechanisms that transform melanocytes into benign melanocytic neoplasms and eventually melanomas. Thus, critical aspects of melanoma pathogenesis may be inferred from patterns of genetic alteration recurrent across subtypes of melanoma and melanocytic neoplasms.
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Acknowledgments
E.H. is grateful for support from NIH grant T32GM007753 (PI: Loren D. Walensky), NIH/NIGMS grant 26260725 (PI: James M. Hogle), the Herchel Smith Fellowship, the Paul and Daisy Soros Fellowship for New Americans, and the Landry Cancer Research Fellowship. L.A.G. is grateful for support from the Howard Hughes Medical Institute. E.H. would like to thank Dr. Ian R. Watson for helpful discussions and suggestions. The current state of knowledge as discussed in this chapter reflects years of work by many individuals and research labs, some of which regrettably could not be cited here due to space limitations. The authors sincerely apologize to those colleagues whose work was not cited.
Disclosure of Potential Conflicts of Interest
E.H. is a consultant for GV. L.A.G. reports receiving a commercial research grant from Novartis, has ownership interest (including patents) in Foundation Medicine, and is a consultant/advisory board member for Warp Drive, Novartis, Boehringer Ingelheim, and Foundation Medicine. L.A.G. is an employee of Eli Lilly and Company.
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Hodis, E., Garraway, L.A. (2019). Molecular Genetics of Melanocytic Neoplasia. In: Fisher, D., Bastian, B. (eds) Melanoma. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7147-9_29
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