Absence of V599E BRAF mutations in desmoplastic melanomas

Authors

  • Jon M. Davison M.D.,

    1. Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
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  • Eli Rosenbaum M.D.,

    1. Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
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  • Terry L. Barrett M.D.,

    1. Department of Dermatology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
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  • David Goldenberg M.D.,

    1. Division of Head and Neck Cancer Research, Department of Otolaryngology, Head and Neck Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland
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  • Mohammad O. Hoque M.D.,

    1. Division of Head and Neck Cancer Research, Department of Otolaryngology, Head and Neck Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland
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  • David Sidransky M.D.,

    1. Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
    2. Division of Head and Neck Cancer Research, Department of Otolaryngology, Head and Neck Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland
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  • William H. Westra M.D.

    Corresponding author
    1. Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
    2. Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
    3. Department of Dermatology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
    4. Division of Head and Neck Cancer Research, Department of Otolaryngology, Head and Neck Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland
    • Department of Pathology, The Weinberg Cancer Center, The Johns Hopkins Hospital, Room 2242, 401 North Broadway, Baltimore, MD 21231
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    • Fax: (410) 955-0115


Abstract

BACKGROUND

Desmoplastic melanoma is an uncommon variant of cutaneous melanoma that mimics soft tissue sarcoma both clinically and morphologically. An activating point mutation of the BRAF oncogene has been identified in a high proportion of conventional cutaneous melanomas, but its frequency in the desmoplastic subtype is not known.

METHODS

The authors tested 12 desmoplastic melanoma specimens for the thymine (T)→adenine (A) missense mutation at nucleotide 1796 of the BRAF gene using a newly developed assay that employs a novel primer extension method. They also tested 57 vertical growth phase cutaneous nondesmoplastic melanoma specimens.

RESULTS

The 1796 T→A mutation was detected in 23 of the 57 conventional cutaneous melanoma specimens but in none of the 12 desmoplastic melanoma specimens (40% vs. 0%; P = 0.0006, Fisher exact 2-tailed test).

CONCLUSIONS

The relative importance of BRAF mutational activation in melanocytic tumorigenesis clearly was not the same across the various subtypes of melanoma, even for melanomas of cutaneous origin that are associated with sun exposure. In contrast to conventional cutaneous melanomas, the desmoplastic variant frequently did not harbor an activating mutation of BRAF. Accordingly, patients with melanomas should not be collectively regarded as a uniform group as new therapeutic strategies are developed that target specific genetic alterations. Cancer 2005. © 2005 American Cancer Society.

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