Distinct gene expression profiles in two cases of Merkel cell polyomavirus-negative Merkel cell carcinoma: shedding light on an esoteric entity

2015 ◽  
Vol 54 (12) ◽  
pp. e549-e551
Author(s):  
Harrison P. Nguyen ◽  
Brent B. Pickrell ◽  
Jaime A. Tschen ◽  
Qin He ◽  
Peter L. Rady ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
Distinct Gene

scholarly journals Distinct Gene Expression Profiles of Viral- and Nonviral-Associated Merkel Cell Carcinoma Revealed by Transcriptome Analysis

2013 ◽  
Vol 133 (4) ◽  
pp. 936-945 ◽  
Author(s):  
Paul W. Harms ◽  
Rajiv M. Patel ◽  
Monique E. Verhaegen ◽  
Thomas J. Giordano ◽  
Kevin T. Nash ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Transcriptome Analysis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Merkel Cell ◽  
Distinct Gene

scholarly journals Merkel Cell Polyomavirus Downregulates N-myc Downstream-Regulated Gene 1, Leading to Cellular Proliferation and Migration

2019 ◽  
Vol 94 (3) ◽  
Author(s):  
Purnima Gupta ◽  
Naveed Shahzad ◽  
Alexis Harold ◽  
Masahiro Shuda ◽  
Assunta Venuti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Carcinoma ◽  
Cellular Proliferation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
T Antigen ◽  
Merkel Cell Polyomavirus ◽  
Early Gene ◽  
Merkel Cell ◽  
Gene Expressing

ABSTRACT Merkel cell polyomavirus (MCPyV) is the first human polyomavirus etiologically associated with Merkel cell carcinoma (MCC), a rare and aggressive form of skin cancer. Similar to other polyomaviruses, MCPyV encodes early T antigen genes, viral oncogenes required for MCC tumor growth. To identify the unique oncogenic properties of MCPyV, we analyzed the gene expression profiles in human spontaneously immortalized keratinocytes (NIKs) expressing the early genes from six distinct human polyomaviruses (PyVs), including MCPyV. A comparison of the gene expression profiles revealed 28 genes specifically deregulated by MCPyV. In particular, the MCPyV early gene downregulated the expression of the tumor suppressor gene N-myc downstream-regulated gene 1 (NDRG1) in MCPyV gene-expressing NIKs and hTERT-MCPyV gene-expressing human keratinocytes (HK) compared to their expression in the controls. In MCPyV-positive MCC cells, the expression of NDRG1 was downregulated by the MCPyV early gene, as T antigen knockdown rescued the level of NDRG1. In addition, NDRG1 overexpression in hTERT-MCPyV gene-expressing HK or MCC cells resulted in a decrease in the number of cells in S phase and cell proliferation inhibition. Moreover, a decrease in wound healing capacity in hTERT-MCPyV gene-expressing HK was observed. Further analysis revealed that NDRG1 exerts its biological effect in Merkel cell lines by regulating the expression of the cyclin-dependent kinase 2 (CDK2) and cyclin D1 proteins. Overall, NDRG1 plays an important role in MCPyV-induced cellular proliferation. IMPORTANCE Merkel cell carcinoma was first described in 1972 as a neuroendocrine tumor of skin, most cases of which were reported in 2008 to be caused by a PyV named Merkel cell polyomavirus (MCPyV), the first PyV linked to human cancer. Thereafter, numerous studies have been conducted to understand the etiology of this virus-induced carcinogenesis. However, it is still a new field, and much work is needed to understand the molecular pathogenesis of MCC. In the current work, we sought to identify the host genes specifically deregulated by MCPyV, as opposed to other PyVs, in order to better understand the relevance of the genes analyzed on the biological impact and progression of the disease. These findings open newer avenues for targeted drug therapies, thereby providing hope for the management of patients suffering from this highly aggressive cancer.

scholarly journals Merkel Cell Polyomavirus Exhibits Dominant Control of the Tumor Genome and Transcriptome in Virus-Associated Merkel Cell Carcinoma

mBio ◽  
2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Gabriel J. Starrett ◽  
Christina Marcelus ◽  
Paul G. Cantalupo ◽  
Joshua P. Katz ◽  
Jingwei Cheng ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Expression Profiles ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
Entire Genome ◽  
Cellular Processes ◽  
Integration Sites ◽  
Somatic Mutagenesis ◽  
Associated Tumors

ABSTRACT Merkel cell polyomavirus is the primary etiological agent of the aggressive skin cancer Merkel cell carcinoma (MCC). Recent studies have revealed that UV radiation is the primary mechanism for somatic mutagenesis in nonviral forms of MCC. Here, we analyze the whole transcriptomes and genomes of primary MCC tumors. Our study reveals that virus-associated tumors have minimally altered genomes compared to non-virus-associated tumors, which are dominated by UV-mediated mutations. Although virus-associated tumors contain relatively small mutation burdens, they exhibit a distinct mutation signature with observable transcriptionally biased kataegic events. In addition, viral integration sites overlap focal genome amplifications in virus-associated tumors, suggesting a potential mechanism for these events. Collectively, our studies indicate that Merkel cell polyomavirus is capable of hijacking cellular processes and driving tumorigenesis to the same severity as tens of thousands of somatic genome alterations. IMPORTANCE A variety of mutagenic processes that shape the evolution of tumors are critical determinants of disease outcome. Here, we sequenced the entire genome of virus-positive and virus-negative primary Merkel cell carcinomas (MCCs), revealing distinct mutation spectra and corresponding expression profiles. Our studies highlight the strong effect that Merkel cell polyomavirus has on the divergent development of viral MCC compared to the somatic alterations that typically drive nonviral tumorigenesis. A more comprehensive understanding of the distinct mutagenic processes operative in viral and nonviral MCCs has implications for the effective treatment of these tumors.

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