Role of Elevated PHIP Copy Number as a Prognostic and … · 1 Role of Elevated PHIP Copy Number as a Prognostic and Progression Marker for Cutaneous Melanoma Vladimir Bezrookove
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1
Role of Elevated PHIP Copy Number as a Prognostic and Progression Marker for
Cutaneous Melanoma
Vladimir Bezrookove 1, Mehdi Nosrati 1, James R. Miller III 1, David De Semir 1, Altaf
A. Dar 1, Elham Vosoughi 1, Edith Vaquero 1, Antje Sucker 3, Alexander J. Lazar 2,
Jeffrey E. Gershenwald 2, Michael A. Davies 2, Dirk Schadendorf 3, Mohammed
Kashani-Sabet 1*
1 Center for Melanoma Research and Treatment, California Pacific Medical Center
(CPMC) Research Institute, San Francisco, CA; 2 Departments of Pathology, Genomic
Medicine, Dermatology & Translational Molecular Pathology, The University of Texas
MD Anderson Cancer Center, Houston, TX; Department of Dermatology, 3 University of
Duisburg-Essen, Essen, Germany, and German Cancer Consortium, Heidelberg,
Germany.
Running title: PHIP copy number in melanoma progression
* Corresponding Author: Mohammed Kashani-Sabet, M.D., California Pacific Medical Center Research Institute, 475 Brannan Street, Suite 130, San Francisco, CA, 94107. Phone: (415) 600-3166, Fax: (415) 600-1719; Email: [email protected] Conflicts of interest: J.R.M. has ownership interests (including patents) at MDMS LLC. J.E.G. has served on advisory boards for Merck, Syndax, and Castle Biosciences. M.A.D. has served on advisory boards for Bristol-Myers Squibb, Roche/Genentech, Novartis, Sanofi-Aventis, Syndax, and Vaccinex, as a consultant for Nanostring (without compensation), and has received grant support from Bristol-Myers Squibb, Roche/Genentech, GSK, Sanofi-Aventis, Oncothyreon, Merck, and Astra Zeneca. D.S. has served on advisory boards for and received honoraria from Bristol-Myers Squibb, Roche, Merck, Incyte, Amgen, Novartis, and EMD. M.K.S. has ownership interest in Melanoma Diagnostics, has received honoraria from Cepheid, and has received grant support from Merck. All other authors declare no conflicts.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
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13. Dummer R, Schadendorf D, Ascierto PA, Arance A, Dutriaux C, Di Giacomo AM, et al. Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2017;18(4):435-45 doi 10.1016/S1470-2045(17)30180-8.
14. Cox OB, Krojer T, Collins P, Monteiro O, Talon R, Bradley A, et al. A poised fragment library enables rapid synthetic expansion yielding the first reported inhibitors of PHIP(2), an atypical bromodomain. Chemical Science 2016;7(3):2322-30 doi 10.1039/C5SC03115J.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
15. Naxerova K, Reiter JG, Brachtel E, Lennerz JK, van de Wetering M, Rowan A, et al. Origins of lymphatic and distant metastases in human colorectal cancer. Science 2017;357(6346):55-60 doi 10.1126/science.aai8515.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791
Published OnlineFirst May 18, 2018.Clin Cancer Res Vladimir Bezrookove, Mehdi Nosrati, James R. Miller, et al. Progression Marker for Cutaneous MelanomaRole of Elevated PHIP Copy Number as a Prognostic and
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Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR-18-0791