Merkel Cell Polyomavirus Strains in Patients with Merkel Cell Carcinoma

Touzé, Antoine; Gaitan, Julien; Maruani, Annabel; Bidre, Emmanuelle Le; Doussinaud, Angélique; Clavel, Christine; Durlach, A.; Aubin, F.; Guyétant, Serge; Lorette, G.; Coursaget, Pierre

doi:10.3201/eid1506.081463

Cited by 68 publications

(77 citation statements)

References 11 publications

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“…This is a major reason for the differences between our data on prevalence and those reported by Loyo et al (7). Certain previous studies reported that MCPyV DNA detection in fresh-frozen tissues is more reliable compared with detection in FFPE samples (20)(21)(22). In this study, low or very low levels of MCPyV DNA were present in a wide variety of oral and maxillofacial tumours and tumour-like lesions, while the reference MCC sample had 1 copy of MCPyV/cell.…”

Section: Discussioncontrasting

confidence: 55%

Low prevalence of Merkel cell polyomavirus with low viral loads in oral and maxillofacial tumours or tumour-like lesions from immunocompetent patients: Absence of Merkel cell polyomavirus-associated neoplasms

Tanio

Matsushita

Kuwamoto

et al. 2015

Molecular and Clinical Oncology

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Abstract. It was recently demonstrated that ~80% of Merkel cell carcinomas (MCCs) harbour a novel polyomavirus, Merkel cell polyomavirus (MCPyV). MCPyV has been detected in various human tissue samples. However, previous studies on the prevalence of MCPyV in oral tumours or tumour-like lesions are incomplete. To address this issue, we measured MCPyV DNA quantity using quantitative polymerase chain reaction (qPCR) in 327 oral tumours or tumour-like lesions and 54 jaw tumours or cyst lesions from 381 immunocompetent patients, as well as in 4 oral lesions from 4 immunosuppressed patients. qPCR revealed a low MCPyV prevalence (25/381, 6.6%) with low viral loads (0.00024-0.026 copies/cell) in oral and maxillofacial tumours and tumour-like lesions from immunocompetent patients. The prevalence was 7/176 (4.0%) in invasive squamous cell carcinomas (SCCs) [2/60 (3.33%) SCCs of the tongue, 4/52 (7.7%) SCCs of the gingiva and 1/19 (5.3%) SCCs of the floor of the mouth], 1/10 (10%) in dysplasias, 1/5 (20%) in adenocarcinomas, 2/13 (15.4%) in adenoid cystic carcinomas,

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Section: Discussioncontrasting

confidence: 55%

Low prevalence of Merkel cell polyomavirus with low viral loads in oral and maxillofacial tumours or tumour-like lesions from immunocompetent patients: Absence of Merkel cell polyomavirus-associated neoplasms

Tanio

Matsushita

Kuwamoto

et al. 2015

Molecular and Clinical Oncology

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“…A high number of VLPs was observed with the VP1 derived from the MKT-21 clone isolated from a French patient with MCC, but only protein aggregates were detected for VP1 proteins derived from clone MCC-350 (4) and MKT-26 (21). It should be noted that coexpression of VP2 did not rescue assembly into VLPs (data not shown).…”

Section: Discussionmentioning

confidence: 91%

“…Amino acid mutations between MCC-350 and MKT-21 were observed at four different positions of the VP1 protein (288, 316, 366, and 422) and between MKT-26 and MKT-21 at two positions (181 and 362) (21). Although no single mutation could be identified as being responsible for the loss of ability to self-assemble into VLPs, the two most plausible explanations are that mutations within the backbone of the VP1 structure (position 181) affect its ability to self-assemble into VLPs, as has been reported for HPV-16 L1 protein (10), or that mutations at the C-terminal part of the MCV VP1 protein (positions 316 to 366) affect the size and shape of VLPs, as reported for simian virus 40 (SV40) (23).…”

Section: Discussionmentioning

confidence: 99%

Generation of Merkel Cell Polyomavirus (MCV)-Like Particles and Their Application to Detection of MCV Antibodies

et al. 2010

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The genome of a new human polyomavirus, known as Merkel cell polyomavirus (MCV), has recently been reported to be integrated within the cellular DNA of Merkel cell carcinoma (MCC), a rare human skin cancer. To investigate MCV seroprevalence in the general population, we expressed three different MCV VP1 in insect cells using recombinant baculoviruses. Viruslike particles (VLPs) were obtained with only one of the three VP1 genes. High-titer antibodies against VP1 VLPs were detected in mice immunized with MCV VLPs, and limited crossreactivity was observed with BK polyomavirus (BKV) and lymphotropic polyomavirus (LPV). MCV antibodies were detected in 77% of the general population, with no variations according to age.Polyomaviruses are small, nonenveloped DNA viruses, with a double-stranded circular DNA genome of ϳ5 kbp packaged within a capsid about 45 nm in diameter. The polyomavirus capsid is composed of three structural proteins: VP1, the major capsid protein, and VP2 and VP3, the minor capsid proteins. Twenty members of the polyomavirus family have been identified to date (24) and, with the exception of the murine pneumotropic polyomavirus and the avian polyomavirus, primary infection is generally asymptomatic. Five polyomaviruses infect humans, including the ubiquitous BK polyomavirus (BKV) and JC polyomavirus (JCV), which cause persistent and/or latent infections and the recently identified KI and WU polyomaviruses isolated from pulmonary secretions (1, 6). A new polyomavirus, the Merkel cell polyomavirus (MCV), was recently discovered in human Merkel cell carcinomas (MCC) (4). MCC is a relatively rare skin cancer in elderly or immunosuppressed patients and is one of the most lethal skin cancers (8). The annual incidence rate of this aggressive primary cutaneous neuroendocrine carcinoma in the United States was reported to be 0.44 per 100,000 inhabitants in 2001 and tripled between 1986 and 2001 (8), and this trend is continuing (7). An incidence of 0.13 cases per 100,000 was recently reported in France (15). Clonal integration of the MCV genome within the tumor genome (4) and the deletions and/or mutations observed within the T antigen gene (17) have suggested a direct oncogenic role for MCV. However, the prevalence and pathogenicity of this newly discovered MCV have yet to be fully investigated.The aim of the study was to produce MCV viruslike particles (VLPs) and to investigate the presence of MCV antibodies in the general population of Europe. MCV VLPs were obtained with only one of the three MCV VP1 strains investigated, and these VLPs were used to investigate cross-reactivity against other polyomaviruses and for the determination of the prevalence of MCV antibodies in the general European population. MATERIALS AND METHODSGeneration of VLPs for MCV, BKV, and LPV polyomaviruses. Expression of the VP1 protein was performed using the MCC350 VP1 prototype sequence and the VP1 sequences amplified from two French MCC patients (MKT-21 and MKT-26) (EMBL FM864207 and FM864209, respectively) (21). MCC350 VP1 codi...

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“…For example, one study detected MCPyV in all 12 cases of MCC when DNA was isolated from fresh frozen tumor specimens and in only 9 of 20 cases when DNA was extracted from FFPE specimens (34). It is likely that the formalin fixation process, longterm storage, and harsh extraction methods of archival MCC specimens reduce the likelihood of detection of MCPyV DNA by qPCR.…”

Section: Discussionmentioning

confidence: 99%

Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirus

Rodig¹,

Cheng²,

Wardzala³

et al. 2012

J. Clin. Invest.

194

176

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Merkel Cell Polyomavirus Strains in Patients with Merkel Cell Carcinoma

Cited by 68 publications

References 11 publications

Low prevalence of Merkel cell polyomavirus with low viral loads in oral and maxillofacial tumours or tumour-like lesions from immunocompetent patients: Absence of Merkel cell polyomavirus-associated neoplasms

Low prevalence of Merkel cell polyomavirus with low viral loads in oral and maxillofacial tumours or tumour-like lesions from immunocompetent patients: Absence of Merkel cell polyomavirus-associated neoplasms

Generation of Merkel Cell Polyomavirus (MCV)-Like Particles and Their Application to Detection of MCV Antibodies

Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirus

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