Clinical relevance of SKP2 alterations in metastatic melanoma

Authors

  • Amy E. Rose,

    1.  Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, USA
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    • Authors contributed equally to the work.

  • Guimin Wang,

    1.  Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, USA
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    • Authors contributed equally to the work.

  • Douglas Hanniford,

    1.  Department of Pathology, New York University School of Medicine, New York, NY, USA
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  • Stefano Monni,

    1.  Division of Biostatistics and Epidemiology, Department of Public Health, Weill Cornell Medical College, New York, NY, USA
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  • Ting Tu,

    1.  Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, USA
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  • Richard L. Shapiro,

    1.  Department of Surgery, New York University School of Medicine, New York, NY, USA
    2.  Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, NY, USA
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  • Russell S. Berman,

    1.  Department of Surgery, New York University School of Medicine, New York, NY, USA
    2.  Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, NY, USA
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  • Anna C. Pavlick,

    1.  Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, NY, USA
    2.  Department of Medicine, New York University School of Medicine, New York, NY, USA
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  • Michele Pagano,

    1.  Department of Pathology, New York University School of Medicine, New York, NY, USA
    2.  Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, NY, USA
    3.  Howard Hughes Medical Institute, Weill Cornell Medical College, New York, NY, USA
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  • Farbod Darvishian,

    1.  Department of Pathology, New York University School of Medicine, New York, NY, USA
    2.  Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, NY, USA
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  • Madhu Mazumdar,

    1.  Division of Biostatistics and Epidemiology, Department of Public Health, Weill Cornell Medical College, New York, NY, USA
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  • Eva Hernando,

    1.  Department of Pathology, New York University School of Medicine, New York, NY, USA
    2.  Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, NY, USA
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  • Iman Osman

    1.  Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, USA
    2.  Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, NY, USA
    3.  Department of Medicine, New York University School of Medicine, New York, NY, USA
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I. Osman, e-mail: iman.osman@nyumc.org

Summary

In this study, we investigated the mechanism(s) of altered expression of protooncogene SKP2 in metastatic melanoma and its clinical relevance in patients with metastatic melanoma. The genomic status of SKP2 was assessed in cell lines by sequencing, single nucleotide polymorphism array, and genomic PCR. Copy number status was then evaluated for concordance with SKP2 mRNA and protein expression. SKP2 protein was further evaluated by immunohistochemistry in 93 human metastatic tissues. No mutations were identified in SKP2. Increased copy number at the SKP2 locus was observed in 6/14 (43%) metastatic cell lines and in 9/22 (41%) human metastatic tissues which was associated with overexpression of SKP2 protein. Overexpression of SKP2 protein in human tissues was associated with worse survival in a multivariate model controlling for the site of metastasis. Copy number gain is a major contributing mechanism of SKP2 overexpression in metastatic melanoma. Results may have implications for the development of therapeutics that target SKP2.

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