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      The Association between MC1R Genotype and BRAF Mutation Status in Cutaneous Melanoma: Findings from an Australian Population

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      Journal of Investigative Dermatology

      Springer Nature

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          Abstract

          There is increasing epidemiological and molecular evidence that cutaneous melanomas arise through multiple causal pathways. The purpose of this study was to explore the relationship between germline and somatic mutations in a population-based series of melanoma patients to reshape and refine the divergent pathway model for melanoma. Melanomas collected from 123 Australian patients were analyzed for melanocortin-1 receptor (MC1R) variants and mutations in the BRAF and NRAS genes. Detailed phenotypic and sun exposure data were systematically collected from all patients. We found that BRAF-mutant melanomas were significantly more likely from younger patients and those with high nevus counts, and were more likely in melanomas with adjacent neval remnants. Conversely, BRAF-mutant melanomas were significantly less likely in people with high levels of lifetime sun exposure. We observed no association between germline MC1R status and somatic BRAF mutations in melanomas from this population. BRAF-mutant melanomas have different origins from other cutaneous melanomas. These data support the divergent pathways hypothesis for melanoma, which may require a reappraisal of targeted cancer prevention activities.

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          Author and article information

          Journal
          Journal of Investigative Dermatology
          Journal of Investigative Dermatology
          Springer Nature
          0022202X
          January 2010
          January 2010
          : 130
          : 1
          : 241-248
          Article
          10.1038/jid.2009.182
          19571821
          © 2010

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