Involvement of Merkel Cell Polyomavirus in the Etiology and Pathogenesis of Merkel Cell Carcinoma: A Systematic Review
Cancer Research Journal
Volume 2, Issue 6-1, December 2014, Pages: 1-10
Received: Nov. 21, 2014; Accepted: Dec. 8, 2014; Published: Dec. 27, 2014
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Authors
Fernando Seiji Morais, Pharmacy Department, Masters Program in Pharmaceutical Sciences, Universidade Estadual do Centro-Oeste (State University of Center-West) (UNICENTRO), Guarapuava-PR, Brazil
Caio Santos Bonilha, Pharmacy Department, Masters Program in Pharmaceutical Sciences, Universidade Estadual do Centro-Oeste (State University of Center-West) (UNICENTRO), Guarapuava-PR, Brazil
Emerson Carraro, Pharmacy Department, Masters Program in Pharmaceutical Sciences, Universidade Estadual do Centro-Oeste (State University of Center-West) (UNICENTRO), Guarapuava-PR, Brazil
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Abstract
Merkel Cell Polyomavirus (MCV) is a virus belonging to the human Polyomavirus family. After its discovery and detection in approximately 80% of Merkel Cell Carcinoma (MCC) tumors, it has been associated with this rare and aggressive skin cancer that primarily affects elderly and immunosuppressed people. In this study, a systematic review was developed to gather and evidence information about the involvement of MCV infection in the development of MCC. An analysis was performed in the PubMed database in order to find articles to answer the purpose of this present study. Ninety-seven articles met the criteria, forty-six of them investigated the prevalence of MCV in MCC clinical samples, and all showed that the MCV-MCC association exists, with the viral presence ranging from 18 to 100% in MCC tumors. In addition, results pointing to the MCV potential carcinogenic, infection, transmission and replication mechanisms, or even possible disease markers or therapeutic evaluations were found. Current literature has demonstrated frequent involvement of MCV in MCC, with survey of some disease indicative laboratory markers and possible therapeutic evaluations.
Keywords
Merkel Cell Carcinoma, Merkel Cell Polyomavirus, Carcinogenesis
To cite this article
Fernando Seiji Morais, Caio Santos Bonilha, Emerson Carraro, Involvement of Merkel Cell Polyomavirus in the Etiology and Pathogenesis of Merkel Cell Carcinoma: A Systematic Review, Cancer Research Journal. Special Issue:Lifestyle and Cancer Risk. Vol. 2, No. 6-1, 2014, pp. 1-10. doi: 10.11648/j.crj.s.2014020601.11
References
[1]
F. Danielsson, et al, “Majority of differentially expressed genes are down-regulated during malignant transformation in a four-stage model,” Proc. Natl. Acad. Sci. USA, vol. 110, no. 17, pp. 6853-6858, April 2013.
[2]
O, Rozenblatt-Rosen, et al, “Interpreting cancer genomes using systematic host perturbations by tumour virus proteins,” Nature. England, vol. 487, no. 7408, pp. 491-495, July 2012.
[3]
A. Kaneda, et al, “Epstein-Barr virus infection as an epigenetic driver of tumorigenesis,” Cancer. Res. USA, vol. 72, no. 14, pp. 3445-3459, July 2012.
[4]
S. W. Jeong, J. Y. Jang, and R. T. Chung, “Hepatitis C virus and hepatocarcinogenesis,” Clin. Mol. Hepatol. Korea, vol. 18, no. 4, pp. 347-356, December 2012.
[5]
A. Jemal, et al, “Annual Report to the Nation on the Status of Cancer, 1975-2009, featuring the burden and trends in human papillomavirus (HPV)-associated cancers and HPV vaccination coverage levels,” J. Natl. Cancer. Inst. USA, vol. 105, no. 3, pp. 175-201, February 2013.
[6]
T. Dalianis and H. H. Hirsch, “Human polyomaviruses in disease and cancer,” Virology. USA, vol. 437, no. 2, pp. 63-72, March 2013.
[7]
D. V. Pastrana, et al, “Positive correlation between Merkel cell polyomavirus viral load and capsid-specific antibody titer,” Med. Microbiol. Immunol. Germany, vol. 201, pp. 17-23, February 2012.
[8]
K. B. Horváth, et al, “A probable etiological role of Merkel cell polyomavirus in the development of Merkel cell carcinoma,”. Orv. Hetil. Hungary, vol. 154, no. 3, pp. 102-112, January 2013.
[9]
C. Toker, “Trabecular carcinoma of the skin,” Arch. Dermatol. USA, vol. 105, pp. 107-110, January 1972.
[10]
M. E. Spurgeon and P. F. Lambert, “Merkel cell polyomavirus: A newly discovered human virus with oncogenic potential,” Virology. USA, vol. 435, no. 1, pp. 118-130, January 2013.
[11]
V. Koljonen, et al, “Chronic lymphocytic leukaemia patients have a high risk of Merkel-cell polyomavirus DNA-positive Merkel-cell carcinoma,” Br. J. Cancer. UK, vol. 101, no. 8, pp. 1444-1447, October 2009.
[12]
J. Albores-Saavedra, et al, “Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study,” J. Cutan. Pathol. USA, vol. 37, no. 1, pp. 20-27, January 2010.
[13]
B. Lemos, P. Nghiem, “Merkel cell carcinoma: more deaths but still no pathway to blame,” J Invest Dermatol. USA, vol. 127, no. 9, pp. 2100-2103, September 2007.
[14]
H. Feng, et al, “Clonal integration of a polyomavirus in human Merkel cell carcinoma,” Science. USA, vol. 319, no. 5866, pp. 1096-1100, February 2008.
[15]
S. Kuwamamoto, et al, “Association of Merkel cell polyomavirus infection with morphologic differences in Merkel cell carcinoma,” Hum. Pathol. USA, vol. 45, no. 2, pp. 632-640, May 2011.
[16]
X. Sastre-Garau, et al, “Merkel cell carcinoma of the skin: pathological and molecular evidence for a causative role of MCV in oncogenesis,” J. Pathol. England, vol. 218, no. 1, pp. 48-56, May 2009.
[17]
K. M. Garneski, et al, Merkel cell polyomavirus is more frequently present in north american than australian Merkel cell carcinoma tumors, J. Invest. Dermatol. USA, vol. 129, no. 1, pp. 246-248, January 2009.
[18]
J. Y. Paik, et al, “Immunohistochemistry for Merkel cell polyomavirus is highly specific but not sensitive for the diagnosis of Merkel cell carcinoma in the Australian population,” Hum. Pathol. USA, vol. 42, no. 10, pp. 1385-1390, October 2011.
[19]
B. Martin, et al, “Merkel cell carcinoma with divergent differentiation: histopathological and immunohistochemical study of 15 cases with PCR analysis for Merkel cell polyomavirus,” Histopathology. England, vol. 65,no. 5, pp. 711-722, April 2013.
[20]
E. J. Duncavage, B.A. Zehnbauer, J.D. Pfeifer, “Prevalence of Merkel cell polyomavirus in Merkel cell carcinoma,” Mod. Pathol. USA, vol. 22, no. 4, pp. 516-521, April 2009.
[21]
L. A. Adhikari, T. H. McCalmont, and A. L. Folpe, “Merkel cell carcinoma with heterologous rhabdomyoblastic differentiation: the role of immunohistochemistry for Merkel cell polyomavirus large T-antigen in confirmation,” J. Cutan. Pathol. USA, vol. 39, no. 1, pp. 47-51, January 2012.
[22]
C. Capella, et al, “Primary gastric Merkel cell carcinoma harboring DNA polyomavirus: first description of an unusual high-gradeneuroendocrine carcinoma,” Hum. Pathol. USA, vol. 45, no. 6, pp. 1310-1314, June 2014.
[23]
B. M. Erovic, “Significant overexpression of the Merkel cell polyomavirus (MCPyV) large T antigen in Merkel cell carcinoma,” Head. Neck. USA, vol. 35, no. 2, pp. 184-189, February 2013.
[24]
H. C. Laude, et al, “Distinct merkel cell polyomavirus molecular features in tumour and non tumour specimens from patients with merkel cell carcinoma,” PLoS. Pathog. USA, vol. 6, no. 8, e1001076, August 2010.
[25]
S. Ota, et al, “Quantitative analysis of viral load per haploid genome revealed the different biological features of Merkel cell polyomavirus infection in skin tumor,” PloS. One. USA, vol. 7, no. 6, e39954, June 2012.
[26]
T. Hattori, et al, “The prevalence of Merkel cell polyomavirus in Japanese patients with Merkel cell carcinoma,”J. Dermatol. Sci. Netherlands, vol. 70, no. 2, pp. 99-107, May 2013.
[27]
J. J. Carter, et al, “Association of Merkel cell polyomavirus – specific antibodies with Merkel cell carcinoma,” J. Natl. Cancer. Inst. USA, vol. 101, no. 21, pp. 1510-1522, November 2009.
[28]
S. J .Rodig, et al, “Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirus,” J. Clin. Invest. USA, vol. 122, no. 12, pp. 4645-4653, December 2012.
[29]
K. G. Paulson, et al, “Antibodies to Merkel cell polyomavirus T antigen oncoproteins reflect tumor burden in Merkel cell carcinoma patients,” Cancer. Res. USA, vol. 70, no. 21, pp. 8388-8397, November 2010.
[30]
A. Touzé, et al, “High levels of antibodies against merkel cell polyomavirus identify a subset of patients with merkel cell carcinoma with better clinical outcome,” J. Clin. Oncol. USA, vol. 29, no. 12, pp. 1612-1619, April 2011.
[31]
H. Faust, et al, “Prospective study of Merkel cell polyomavirus and risk of Merkel cell carcinoma,” Int. J. Cancer. USA, vol. 134, no. 4, pp. 844-848, February 2014.
[32]
C. Andres, et al, “Prevalence of MCPyV in Merkel cell carcinoma and non-MCC tumors,” J. Cutan. Pathol. USA, vol. 7, no. 1, pp. 28-34, January 2010.
[33]
C. Andres, et al, “Immunohistochemical features of Merkel cell carcinoma in correlation with presence of Merkel cell polyomavirus DNA,” Acta. Derm. Venereol. Sweden, vol. 91, no. 6, pp. 722-723, October, 2011.
[34]
M. Shuda, et al, “Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissuesand lymphoid tumors,” Int. J. Cancer. USA, vol. 125, no. 6, pp. 1243-1249, September 2009.
[35]
V. Foulongne, et al, “Merkel cell polyomavirus DNA detection in lesional and nonlesional skin from patients with Merkel cell carcinoma or other skin diseases,” Br. J. Dermatol. UK, vol. 162, no. 1, pp. 59-63, January 2010.
[36]
U. Wieland, et al, “Merkel cell polyomavirus DNA in persons without Merkel cell carcinoma,” Emerg. Infect. Dis. USA, vol. 15, no. 9, pp. 1496-1498, September 2009.
[37]
Y. L. Tolstov, et al, “Asymptomatic primary Merkel cell polyomavirus infection among adults,” Emerg. Infect. Dis. USA, vol. 17, no. 8, pp. 1371-1380, August 2011.
[38]
T. F. Schulz, “Cancer and viral infections in immunocompromised individuals,” Int. J. Cancer. USA, vol. 125, no. 8, pp. 1755-1763, October 2009.
[39]
J. G. Lyer, et al, “Merkel cell polyomavirus-specific CD8⁺ and CD4⁺ T-cell responses identified in Merkel cell carcinomas and blood,” Clin. Cancer. Res. USA, vol. 17, no. 21, pp. 6671-6680, November 2011.
[40]
M. Li, et al, “Metastatic Merkel cell carcinoma of the oral cavity in a human immunodeficiency virus-positive patient and the detection of Merkel cell polyomavirus,” Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol. USA, vol. 115, no. 5,pp. 66-71, May 2013.
[41]
M. Loyo, et al, “Quantitative detection of Merkel cell virus in human tissues and possible mode of transmission,” Int. J. Cancer. USA, vol. 126, no. 12, pp. 2991-2996, June 2010.
[42]
D. Bzhalava, et al, “Risk of second cancers after the diagnosis of Merkel cell carcinoma in Scandinavia,” Br. J. Cancer. England, vol. 104, no. 1, pp. 178-180, January 2011.
[43]
K. Bhatia, “Merkel cell carcinoma subgroups by Merkel cell polyomavirus DNA relative abundance and oncogene expression,” Int. J. Cancer. USA, vol. 126, no. 9, pp. 2240-2246, May 2010.
[44]
K. N. Wu, “Detection of Merkel cell carcinoma polyomavirus in mucosal Merkel cell carcinoma,” Int. J. Surg. Pathol. USA, vol. 18, no. 5, pp. 342-346, October 2010.
[45]
C. T. Wetzels, et al, “Ultrastructural proof of polyomavirus in Merkel cell carcinoma tumour cells and its absence in small cell carcinoma of the lung,” PloS. One. USA, vol. 4, no. 3, e4958, March 2009.
[46]
D. de Biase, et al, “Extracutaneous Merkel cell carcinomas harbor polyomavirus DNA,” Hum. Pathol. USA, vol. 43, no. 7, pp. 980-985, July 2012.
[47]
D. Schrama, et al, “Distinction of 2 different primary Merkel cell carcinomas in 1 patient by Merkel cell polyomavirus genome analysis,” Arch. Dermatol. USA, vol. 146, no.6, pp. 687-689, June 2010.
[48]
K. Kaibuchi-Noda, et al, “Detection of Merkel cell polyomavirus in cutaneous squamous cell carcinoma before occurrence of Merkel cell carcinoma,” J. Am. Acad. Dermatol. USA, vol. 65, no. 5, pp. 152-154, November 2011.
[49]
D. M. Reisinger, et al, “Lack of evidence for basal or squamous cell carcinoma infection with Merkel cell polyomavirus in immunocompetent patients with Merkel cell carcinoma,” J. Am. Acad. Dermatol. USA, vol. 63, no. 3, pp. 400-403, September 2010.
[50]
T. Iwasaki, et al, “Merkel cell polyomavirus infection in both components of a combined Merkel cell carcinoma and basal cell carcinoma with ductal differentiation; each component had a similar but different novel Merkel cell polyomavirus large T antigen truncating mutation,” Hum. Pathol. USA, vol. 44, no. 3, pp. 442-447, March 2013.
[51]
M. Imajoh, et al, “Novel human polyomaviruses, Merkel cell polyomavirus and human polyomavirus 9, in Japanese chronic lymphocytic leukemia cases,” J. Hematol. Oncol. England, vol. 5, pp. 25-29, June 2012.
[52]
W. R. Oliveira, et al, “Merkel cell polyomavirus in Merkel cell carcinoma from a Brazilian epidermodysplasia verruciformis patient,” J. Am. Acad. Dermatol. USA, vol. 62, no. 5, pp. 889-890, May 2010.
[53]
M. Matsushita, et al, “Detection of Merkel cell polyomavirus in the human tissues from 41 Japanese autopsy cases using polymerase chain reaction,”Intervirology. Switzerland, vol. 56, no. 1, pp. 1-5, September 2013.
[54]
H. Katano, et al, “Detection of Merkel cell polyomavirus in Merkel cell carcinoma and Kaposi's sarcoma,” J. Med. Virol. USA, vol. 81, no. 11, pp. 1951-1958, November 2009.
[55]
T. Y. Ly, N. M. Walsh, and S. Pasternak, et al, “The spectrum of Merkel cell polyomavirus expression in Merkel cell carcinoma, in a variety of cutaneous neoplasms, and in neuroendocrine carcinomas from different anatomical sites,” .Hum. Pathol. USA, vol. 43, no. 4, pp. 557-566, April 2012.
[56]
K. A. Haitz, et al, “Merkel cell polyomavirus DNA detection in a patient with Merkel cell carcinoma and multiple other skin cancers,” Int. J. Dermatol. USA, vol. 51, no. 4, pp. 442-444, April 2012.
[57]
K. J. Busam, et al, “Merkel cell polyomavirus expression in merkel cell carcinomas and its absence in combined tumors and pulmonary neuroendocrine carcinomas,” Am. J. Surg. Pathol. USA, vol. 33, no. 9, pp. 1378-1385, September 2009.
[58]
H. S. Jung, et al, “Detection of Merkel cell polyomavirus in Merkel cell carcinomas and small cell carcinomas by PCR and immunohistochemistry,” Histol. Histopathol. Spain, vol. 26, no. 10, pp. 1231-1241, October 2011.
[59]
J, Mangana, et al, “Prevalence of Merkel cell polyomavirus among Swiss Merkel cell carcinoma patients,” Dermatology. Switzerland, vol. 221, no. 2, pp. 184-188, August 2010.
[60]
C. Mitteldorf, et al, “Detection of Merkel cell polyomavirus and human papillomaviruses in Merkel cell carcinoma combined with squamous cell carcinoma in immunocompetent European patients,” Am. J. Dermatopathol. USA, vol. 34, no. 5, pp. 506-510, July 2012.
[61]
M. Sadeghi,.et al, “Newly discovered KI, WU, and Merkel cell polyomaviruses: no evidence of mother-to-fetus transmission,” Virol. J. England, vol. 7, pp. 251, September 2010.
[62]
N. Fischer, et al, “Detection of Merkel cell polyomavirus (MCPyV) in Merkel cell carcinoma cell lines: cell morphology and growth phenotype do not reflect presence of the virus,” Int. J. Cancer. USA, vol. 126, no. 9, pp. 2133-2142, May 2010.
[63]
H. Sihto, et al, “Clinical factors associated with Merkel cell polyomavirus infection in Merkel cell carcinoma,”. J. Natl. Cancer. Inst. USA, vol. 101, no. 13, pp. 938-945, July 2009.
[64]
U. Neu, et al, “Structures of Merkel cell polyomavirus VP1 complexes define a sialic acid binding site required for infection,” PLoS. Pathog. USA, vol. 8, no. 7, e1002738, Jly 2012.
[65]
H. Feng, et al, “Cellular and viral factors regulating Merkel cell polyomavirus replication,” PLoS. One. USA, vol. 6, no. 7, e22468, July 2011.
[66]
S. K. Demetriou, et al, “Defective DNA repair and cell cycle arrest in cells expressing Merkel cell polyomavirus T antigen,” Int. J. Cancer. USA, vol.131, no. 8, pp. 1818-1827, October 2012.
[67]
C. Willmes, et al, “Type I and II IFNs inhibit Merkel cell carcinoma via modulation of the Merkel cell polyomavirus T antigens,” Cancer. Res. USA, vol. 72, no. 8, pp. 2120-2128, April 2012.
[68]
J. Cheng, et al, “Merkel cell polyomavirus large T antigen has growth-promoting and inhibitory activities,” J. Virol. USA, vol 87, no. 11, pp. 6118-6126, June 2013.
[69]
M. Shuda, et al, “T antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus,” Proc. Natl. Acad. Sci. USA, vol. 105, no. 42, pp. 16272-16277, October 2008.
[70]
C. Martel-Jantin, et al, “Genetic variability and integration of Merkel cell polyomavirus in Merkel cell carcinoma,”Virology. USA, vol. 426, no. 2, pp. 134-142, May 2012.
[71]
T. Nakamura, et al, “Nuclear localization of Merkel cell polyomavirus large T antigen in Merkel cell carcinoma,” Virology. USA, vol. 398, no. 2, pp. 273-279, March 2010.
[72]
J. Li, et al, “Merkel cell polyomavirus large T antigen disrupts host genomic integrity and inhibits cellular proliferation,” J. Virol. USA, vol. 17, no. 16, pp. 9173-9188, August 2013.
[73]
A. Kassem, et al, “Frequent detection of Merkel cell polyomavirus in human Merkel cell carcinomas and identification of a unique deletion in the VP1 gene,” Cancer. Res. USA, vol. 68, no. 13, pp. 5009-5013, July 2008.
[74]
A. Mogha, et al, “Merkel cell polyomavirus small T antigen mRNA level is increased following in vivo UV-radiation,” PLoS. One. USA, vol. 5, no. 7, e11423, July 2010.
[75]
X, Wang, et al, “Bromodomain protein Brd4 plays a key role in Merkel cell polyomavirus DNA replication,” PLoS. Pathog. USA, vol. 8, no. 8, e1003021, November 2012.
[76]
R. Houben, et al, “An intact retinoblastoma protein-binding site in Merkel cell polyomavirus large T antigen is required for promoting growth of Merkel cell carcinoma cells,” Int. J. Cancer. USA, vol. 130, no. 4, pp. 847-856, February 2012.
[77]
S. Borchert, et al, “High-affinity Rb binding, p53 inhibition, subcellular localization, and transformation by wild-type or tumor-derived shortened Merkel cell polyomavirus large T antigens,” J. Virol. USA, vol. 88, no. 6, pp. 3144-3160, March 2014.
[78]
S. H. Tsang, et al, “Host DNA damage response factors localize to merkel cell polyomavirus DNA replication sites to support efficient viral DNA replication,” J. Virol. USA, vol. 88, no. 6, pp. 3285-3297, March 2014.
[79]
N. Shahzad, et al, “The T antigen locus of Merkel cell polyomavirus downregulates human Toll-like receptor 9 expression,” USA, vol. 87, no. 23, pp. 13009-13019, December 2013.
[80]
J. Handschel, et al, “The new polyomavirus (MCPyV) does not affect the clinical course in MCCs,” Int. J. Oral. Maxillofac. Surg. Denmark, vol. 39, no. 11, pp. 1086-1090, November 2010.
[81]
D. Schrama, et al, “Merkel cell polyomavirus status is not associated with clinical course of Merkel cell carcinoma,” J. Invest. Dermatol. USA, vol. 131, no. 8, pp. 1631-1638, August 2011.
[82]
H. Higaki-Mori, et al, “Association of Merkel cell polyomavirus infection with clinicopathological differences in Merkel cell carcinoma,” Hum. Pathol. USA, vol. 43, no. 12, pp. 2282-2291, December 2012.
[83]
T. Iwasaki, et al, “Usefulness of significant morphologic characteristics in distinguishing between Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative Merkel cell carcinomas,” Hum. Pathol. USA, vol. 44, no. 9, pp. 1912-1917, September 2013.
[84]
R. Houben, et al, “Merkel cell polyomavirus-infected Merkel cell carcinoma cells require expression of viral T antigens,” J. Virol. USA, vol. 84, no. 14, pp. 7064-7072, July 2010.
[85]
H. Sihto, “Merkel polyomavirus infection, large T antigen, retinoblastoma protein and outcome in Merkel cell carcinoma,” Clin. Cancer. Res. USA, vol. 17, no. 14, pp. 4806-4813, July 2011.
[86]
P. W. Harms, et al, “Distinct gene expression profiles of viral- and nonviral-associated merkel cell carcinoma revealed by transcriptome analysis,” J. Invest. Dermatol. USA, vol. 133, no. 4, pp. 936-945, April 2013.
[87]
R. Houben, et al, “Comparable expression and phosphorylation of the retinoblastoma protein in Merkel cell polyoma virus-positive and negative Merkel cell carcinoma,” Int. J. Cancer. USA, vol. 126, no. 3, pp. 796-798, February 2010.
[88]
R. Arora, et al, “Survivin is a therapeutic target in Merkel cell carcinoma,” Sci. Transl. Med. USA, vol. 4, no. 133, pp. 133-156, May 2012.
[89]
K. E. Fleming, et al, “Support for p63 expression as an adverse prognostic marker in Merkel cell carcinoma: report on a canadian cohort,” Hum. Pathol. USA, vol. 45, no. 5, pp. 952-960, May 2014.
[90]
B. J. Hall, et al, “Immunohistochemical prognostication of Merkel cell carcinoma: p63 expression but not polyomavirus status correlates with outcome,” J. Cutan. Pathol. USA, vol. 39, no. 10, pp. 911-917, October 2012.
[91]
M. Waltari, et al, “Association of Merkel cell polyomavirus infection with tumor p53, KIT, stem cell factor, PDGFR-alpha and survival in Merkel cell carcinoma,” Int. J. Cancer. USA, vol. 129, no. 3, pp. 619-628, August 2011.
[92]
R. Houben, et al, “Mechanisms of p53 restriction in Merkel cell carcinoma cells are independent of the Merkel cell polyoma virus T antigens,” J. Invest. Dermatol. USA, vol. 133, no. 10, pp. 2453-2460, October 2013.
[93]
M. Shuda, et al, “Human Merkel cell polyomavirus small T antigen is an oncoprotein targeting the 4E-BP1 translation regulator,” J. Clin. Invest. USA, vol. 121, no. 9, pp. 3623-3634, September 2011.
[94]
S. Argermeyer, et al, “Merkel cell polyomavirus–positive Merkel cell carcinoma cells do not require expression of the viral small T antigen,” J. Invest. Dermatol. USA, vol 133, no. 8, pp. 2059-2064, August 2013.
[95]
H. Nakajima, et al, “Screening of the specific polyoma virus as diagnostic and prognostic tools for Merkel cell carcinoma,” J. Dermatol. Sci. Netherlands, vol. 56, no. 3, December 2009.
[96]
R. Houben, et al, “Merkel cell carcinoma and Merkel cell polyomavirus: evidence for hit-and-run oncogenesis,” J. Invest. Dermatol. USA, vol. 132, no. 1, pp. 254-256, January 2012.
[97]
H. J. Kwun, et al, “Merkel cell polyomavirus small T antigen controls viral replication and oncoprotein expression by targeting the cellular ubiquitin ligase SCFFbw7,” Cell. Host. Microbe. USA, vol. 14, no. 2, pp. 125-135, August 2013.
[98]
M. Shuda, et al, “Human Merkel cell polyomavirus small T antigen is an oncoprotein targeting the 4E-BP1 translation regulator,” J. Clin. Invest. USA, vol. 121, no. 9, pp. 3623-3634, September 2011.
[99]
M. Shuda, Y. Chang, P.S. Moore, “Merkel cell polyomavirus-positive Merkel cell carcinoma requires viral small T-antigen for cell proliferation,” J. Invest. Dermatol. USA, vol. 134, no. 5, pp. 1479-1481, May 2014.
[100]
M. Matsushita, et al, “A new in situ hybridization and immunohistochemistry with a novel antibody to detect small T-antigen expressions of Merkel cell polyomavirus (MCPyV),” Diagn. Pathol. England, vol. 9, p. 65, March 2014.
[101]
H. Xie, et al, “MicroRNA expression patterns related to merkel cell polyomavirus infection in human merkel cell carcinoma,” J. Invest. Dermatol. USA, vol. 134, no. 2, pp. 507-517, February 2014.
[102]
L. R. Dresang, et al, “Response of Merkel cell polyomavirus-positive merkel cell carcinoma xenografts to a surviving inhibitor,” PloS. One. USA, vol. 8, no. 11, e80543, November 2013.
[103]
C. Hafner, et al, “Activation of the PI3K/AKT pathway in Merkel cell carcinoma,” PLoS. One. USA, vol. 7, no. 2, pp. e31225, February 2012.
[104]
C. Andres, et al, “Re: Clinical factors associated with Merkel cell polyomavirus infection in Merkel cell carcinoma,” J. Natl. Cancer. Inst. USA, vol. 101, no. 23, pp. 1955-1956, December 2009.
[105]
B. Akgül, et al, “Lack of integrin β5 in Merkel cell carcinomas and derived cell lines is frequently associated with Merkel cell polyomavirus positivity,” J. Dermatol. Sci. Netherlands, vol. 67, no. 1, pp. 66-68, July 2012.
[106]
J. C. Becker, et al, “MC polyomavirus is frequently present in Merkel cell carcinoma of european patients,” J. Invest. Dermatol. USA, vol. 129, no. 1, pp. 248-250, January 2009.
[107]
E. Varga, et al, “Detection of Merkel cell polyomavirus DNA in Merkel cell carcinomas,” Br. J. Dermatol. UK, vol. 161, no. 4, pp. 930-932, October 2009.
[108]
F. Paolini, et al, “Merkel cell polyomavirus in Merkel cell carcinoma of Italian patients,” Virol. J. England, vol. 8, pp. 103, March 2011.
[109]
E. Perez-Ramirez and U. Höfl e, “Merkel cell polyomavirus and Merkel cell carcinoma, France,” Emerg. Infect. Dis. USA, vol. 14, no.9, pp. 1491-1493, September 2008.
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