Abstract
The complex epidemiology of melanoma, variety of histologic subtypes, and presence of different genetic alterations has indicated for some time that melanoma is a heterogeneous disease. Subgroups of melanomas may develop along specific pathways resulting in complex risk factors, prognostic heterogeneity, and differing responses to treatments. Understanding and developing biomarkers for these pathways will be crucial for implementing appropriate interventions. Somatic alterations that are associated with these specific pathways include BRAF and NRAS mutations, which are mutually exclusive of each other, defining three melanoma subgroups (BRAF+/NRAS−, BRAF−NRAS+, and BRAF−/NRAS‐). Number of nevi and ability to tan are associated with BRAF+ melanomas, while NRAS+ melanomas are also associated with number of nevi. BRAF−/NRAS− melanomas are associated with markers of chronic sun exposure, and exploration is under way to determine if BRAF+ and NRAS+ melanomas are associated with intermittent sun exposure and/or exposure at different ages. Melanocortin‐1 receptor (MC1R) polymorphisms have been associated with BRAF‐mutant melanoma in two Italian populations but not consistently in other populations. KIT mutations are also of interest and may define an additional pathway associated, in particular, with mucosal melanomas. These findings have strong implications for both targeted prevention and therapies, which could impact melanoma incidence and survival.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):CN12-05.
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