A human polyomavirus was recently discovered in Merkel cell carcinoma (MCC) specimens. The Merkel cell polyomavirus (MCPyV) genome undergoes clonal integration into the host cell chromosomes of MCC tumors and expresses small T antigen and truncated large T antigen. Previous studies have consistently reported that MCPyV can be detected in approximately 80% of all MCC tumors. We sought to increase the sensitivity of detection of MCPyV in MCC by developing antibodies capable of detecting large T antigen by immunohistochemistry. In addition, we expanded the repertoire of quantitative PCR primers specific for MCPyV to improve the detection of viral DNA in MCC. Here we report that a novel monoclonal antibody detected MCPyV large T antigen expression in 56 of 58 (97%) unique MCC tumors. PCR analysis specifically detected viral DNA in all 60 unique MCC tumors tested. We also detected inactivating point substitution mutations of TP53 in the two MCC specimens that lacked large T antigen expression and in only 1 of 56 tumors positive for large T antigen. These results indicate that MCPyV is present in MCC tumors more frequently than previously reported and that mutations in TP53 tend to occur in MCC tumors that fail to express MCPyV large T antigen.
Scott J. Rodig, Jingwei Cheng, Jacek Wardzala, Andrew DoRosario, Jessica J. Scanlon, Alvaro C. Laga, Alejandro Martinez-Fernandez, Justine A. Barletta, Andrew M. Bellizzi, Subhashini Sadasivam, Dustin T. Holloway, Dylan J. Cooper, Thomas S. Kupper, Linda C. Wang, James A. DeCaprio
Title and authors | Publication | Year |
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Merkel polyomavirus-specific T cells fluctuate with merkel cell carcinoma burden and express therapeutically targetable PD-1 and Tim-3 exhaustion markers
OK Afanasiev, L Yelistratova, N Miller, K Nagase, K Paulson, JG Iyer, D Ibrani, DM Koelle, P Nghiem |
Clinical cancer research | 2013 |
Tumor-specific T cells in human Merkel cell carcinomas: a possible role for Tregs and T cell exhaustion in reducing T cell responses
M Dowlatshahi, V Huang, A Gehad, Y Jiang, A Calarese, JE Teague, A Dorosario, J Cheng, P Nghiem, C Schanbacher, M Thakuria, C Schmults, LC Wang, RA Clark |
Journal of Investigative Dermatology | 2013 |
Regression of Metastatic Merkel Cell Carcinoma Following Transfer of Polyomavirus-Specific T Cells and Therapies Capable of Reinducing HLA Class-I
AG Chapuis, OK Afanasiev, JG Iyer, KG Paulson, U Parvathaneni, JH Hwang, I Lai, IM Roberts, HL Sloan, S Bhatia, KC Shibuya, T Gooley, C Desmarais, DM Koelle, C Yee, P Nghiem |
Cancer immunology research | 2013 |
A cornucopia of human polyomaviruses
JA DeCaprio, RL Garcea |
Nature Reviews Microbiology | 2013 |
Merkel cell polyomavirus large T antigen disrupts host genomic integrity and inhibits cellular proliferation
J Li, X Wang, J Diaz, SH Tsang, CB Buck, J You |
Journal of virology | 2013 |
Merkel cell polyomavirus large T antigen has growth-promoting and inhibitory activities
J Cheng, O Rozenblatt-Rosen, KG Paulson, P Nghiem, JA DeCaprio |
Journal of virology | 2013 |
MicroRNA Expression Patterns Related to Merkel Cell Polyomavirus Infection in Human Merkel Cell Carcinoma
H Xie, L Lee, S Caramuta, A Höög, N Browaldh, V Björnhagen, C Larsson, WO Lui |
Journal of Investigative Dermatology | 2013 |
Different serologic behavior of MCPyV, TSPyV, HPyV6, HPyV7 and HPyV9 polyomaviruses found on the skin
E der Meijden, S Bialasiewicz, RJ Rockett, SJ Tozer, TP Sloots, MC Feltkamp |
PloS one | 2013 |
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KC Hourdequin, JA Lefferts, JB Brennick, MS Ernstoff, GJ Tsongalis, JM Pipas |
Oncology Letters | 2013 |
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NJ Miller, S Bhatia, U Parvathaneni, JG Iyer, P Nghiem |
Current Treatment Options in Oncology | 2013 |
Palliative treatment for in-transit cutaneous metastases of Merkel cell carcinoma using surface-mold computer-optimized high-dose-rate brachytherapy
L Garibyan, SE Cotter, JL Hansen, C Noell, A Dorosario, DA O’Farrell, PM Devlin, LC Wang |
The Cancer Journal | 2013 |
PD-L1 Expression in the Merkel Cell Carcinoma Microenvironment: Association with Inflammation, Merkel Cell Polyomavirus, and Overall Survival
EJ Lipson, JG Vincent, M Loyo, LT Kagohara, BS Luber, H Wang, H Xu, SK Nayar, TS Wang, D Sidransky, RA Anders, SL Topalian, JM Taube |
Cancer immunology research | 2013 |