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Merkel cell polyomavirus and human papilloma virus in proliferative skin lesions arising in patients treated with BRAF inhibitors

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Abstract

The potential role of oncogenic viruses mediating development of proliferative skin lesions in patients treated with RAF inhibitors is poorly understood. The objective of this study was to investigate human papilloma virus (HPV) and Merkel cell polyomavirus (MCPyV) in skin lesions among patients treated with RAF inhibitors with the help of a case series describing prevalence of HPV, MCPyV, and RAS mutations in skin biopsies obtained from patients receiving RAF inhibitors and developing cutaneous lesions. HPV-DNA was amplified by PCR utilizing multiple nested primer systems designed for detection of a broad range of HPV types. MCPyV copy number determination with real time PCR technology was performed by a “Quantification of MCPyV, small t region” kit. Thirty-six patients were tested (squamous cell carcinoma (SCC) = 14; verruca vulgaris = 15; other = 11). Nine of 12 SCCs (75 %) and eight of 13 verruca vulgaris lesions (62 %) tested positive for MCPyV whereas none of the normal skin biopsies obtained from nine of these patients tested positive for MCPyV (p = 0.0007). HPV incidence in cutaneous SCCs was not different compared to normal skin (50 vs. 56 %, p = 0.86). The association between MCPyV and proliferative skin lesions after RAF inhibitor therapy merits further investigation.

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Acknowledgments

We would like to thank Eucharia Iwuanyanwu, Tiffiny Jackson, Shobha Pai, Amy Patel, and Tamara Barnes for their expert assistance in performing skin punch biopsies. We would like to thank Adrienne Howard with her assistance with regulatory considerations. We would like to thank Qin He and Rebecca Simonette for their expert help with the molecular biological experiments. This work was supported by the NIH Clinical and Translational Science Award UL1 RR024148 and by the NIH Cancer Center Support Grant (CCSG) award CA016672 to MD Anderson Cancer Center.

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Authors and Affiliations

  1. Sarah Cannon Research Institute, 1800 Williams Street, Suite 300, Denver, CO, 80218, USA

    G. S. Falchook

  2. Department of Dermatology, The University of Texas Health Science Center at Houston, Houston, TX, USA

    P. Rady & S. K. Tyring

  3. Baylor College of Medicine, Houston, TX, USA

    J. C. Konopinski & H. P. Nguyen

  4. Division of Internal Medicine, Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    N. Busaidy & S. Sherman

  5. Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    K. Hess

  6. Division of Internal Medicine, Department of Dermatology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    S. Hymes

  7. Division of Pathology and Laboratory Medicine, Departments of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    V. G. Prieto

  8. Florida Cancer Specialists, Orlando, FL, USA

    E. Bustinza-Linares

  9. Division of Cancer Medicine, Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Q. Lin, K. L. Parkhurst & D. S. Hong

  10. Moores Cancer Center, University of California San Diego, La Jolla, CA, USA

    R. Kurzrock

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  1. G. S. Falchook
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  2. P. Rady
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Correspondence to G. S. Falchook.

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Conflict of interest

Naifa Busaidy received research grant funding from Bayer-Onyx. Steven Sherman was a consultant for Bayer, Roche, and Plexxikon. Gerald Falchook received research funding and travel reimbursement for conference attendance from GlaxoSmithKline. The other coauthors report no conflicts of interest.

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This work was conducted in Houston, Texas, USA with approval of the Institutional Review Board of MD Anderson Cancer Center.

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Falchook, G.S., Rady, P., Konopinski, J.C. et al. Merkel cell polyomavirus and human papilloma virus in proliferative skin lesions arising in patients treated with BRAF inhibitors. Arch Dermatol Res 308, 357–365 (2016). https://doi.org/10.1007/s00403-016-1650-y

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  • DOI: https://doi.org/10.1007/s00403-016-1650-y

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