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BRAF mutations in cutaneous melanoma are independently associated with age, anatomic site of the primary tumor, and the degree of solar elastosis at the primary tumor site

Authors

  • Jürgen Bauer,

    1.  Department of Dermatology, Eberhard Karls University, Tübingen, Germany
    2.  Department of Dermatology, University of California at San Francisco, San Francisco, CA, USA
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    • These authors contributed equally to the work.

  • Petra Büttner,

    1.  School of Public Health, Tropical Medicine and Rehabilitation Sciences, James Cook University, Townville, Qld, Australia
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    • These authors contributed equally to the work.

  • Rajmohan Murali,

    1.  Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney Medical School, The University of Sydney, Melanoma Institute Australia, NSW, Australia
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    • These authors contributed equally to the work.

  • Ichiro Okamoto,

    1.  Department of Dermatology, University of Vienna Medical School, Vienna, Austria
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  • Nicholas A. Kolaitis,

    1.  Department of Dermatology, University of California at San Francisco, San Francisco, CA, USA
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  • Maria T. Landi,

    1.  Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA
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  • Richard A. Scolyer,

    1.  Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney Medical School, The University of Sydney, Melanoma Institute Australia, NSW, Australia
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  • Boris C. Bastian

    1.  Department of Dermatology, University of California at San Francisco, San Francisco, CA, USA
    2.  Departments of Dermatology and Pathology and UCSF Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA
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Boris C. Bastian, e-mail: bastianb@mskcc.org

Summary

Oncogenic BRAF mutations are more frequent in cutaneous melanoma occurring at sites with little or moderate sun-induced damage than at sites with severe cumulative solar ultraviolet (UV) damage. We studied cutaneous melanomas from geographic regions with different levels of ambient UV radiation to delineate the relative effects of cumulative UV damage, age, and anatomic site on the frequency of BRAF mutations. We show that BRAF-mutated melanomas occur in a younger age group on skin without marked solar elastosis and less frequently affect the head and neck area, compared to melanomas without BRAF mutations. The findings indicate that BRAF-mutated melanomas arise early in life at low cumulative UV doses, whereas melanomas without BRAF mutations require accumulation of high UV doses over time. The effect of anatomic site on the mutation spectrum further suggests regional differences among cutaneous melanocytes.

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