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Distinct merkel cell polyomavirus molecular features in tumour and non tumour specimens from patients with merkel cell carcinoma.

ABSTRACT: Merkel Cell Polyomavirus (MCPyV) is associated with Merkel Cell carcinoma (MCC), a rare, aggressive skin cancer with neuroendocrine features. The causal role of MCPyV is highly suggested by monoclonal integration of its genome and expression of the viral large T (LT) antigen in MCC cells. We investigated and characterized MCPyV molecular features in MCC, respiratory, urine and blood samples from 33 patients by quantitative PCR, sequencing and detection of integrated viral DNA. We examined associations between either MCPyV viral load in primary MCC or MCPyV DNAemia and survival. Results were interpreted with respect to the viral molecular signature in each compartment. Patients with MCC containing more than 1 viral genome copy per cell had a longer period in complete remission than patients with less than 1 copy per cell (34 vs 10 months, P = 0.037). Peripheral blood mononuclear cells (PBMC) contained MCPyV more frequently in patients sampled with disease than in patients in complete remission (60% vs 11%, P = 0.00083). Moreover, the detection of MCPyV in at least one PBMC sample during follow-up was associated with a shorter overall survival (P?= 0.003). Sequencing of viral DNA from MCC and non MCC samples characterized common single nucleotide polymorphisms defining 8 patient specific strains. However, specific molecular signatures truncating MCPyV LT were observed in 8/12 MCC cases but not in respiratory and urinary samples from 15 patients. New integration sites were identified in 4 MCC cases. Finally, mutated-integrated forms of MCPyV were detected in PBMC of two patients with disseminated MCC disease, indicating circulation of metastatic cells. We conclude that MCPyV molecular features in primary MCC tumour and PBMC may help to predict the course of the disease.

SUBMITTER: Laude HC

PROVIDER: S-EPMC2928786 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Distinct merkel cell polyomavirus molecular features in tumour and non tumour specimens from patients with merkel cell carcinoma.

Laude Hélène C HC Jonchère Barbara B Maubec Eve E Carlotti Agnès A Marinho Eduardo E Couturaud Benoit B Peter Martine M Sastre-Garau Xavier X Avril Marie-Françoise MF Dupin Nicolas N Rozenberg Flore F

PLoS pathogens 20100826 8

Merkel Cell Polyomavirus (MCPyV) is associated with Merkel Cell carcinoma (MCC), a rare, aggressive skin cancer with neuroendocrine features. The causal role of MCPyV is highly suggested by monoclonal integration of its genome and expression of the viral large T (LT) antigen in MCC cells. We investigated and characterized MCPyV molecular features in MCC, respiratory, urine and blood samples from 33 patients by quantitative PCR, sequencing and detection of integrated viral DNA. We examined associ ...[more]

PMID: 20865165

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Project description:BackgroundMerkel cell polyomavirus (MCPyV) has been detected in approximately 75% of patients with the rare skin cancer Merkel cell carcinoma. We investigated the prevalence of antibodies against MCPyV in the general population and the association between these antibodies and Merkel cell carcinoma.MethodsMultiplex antibody-binding assays were used to assess levels of antibodies against polyomaviruses in plasma. MCPyV VP1 antibody levels were determined in plasma from 41 patients with Merkel cell carcinoma and 76 matched control subjects. MCPyV DNA was detected in tumor tissue specimens by quantitative polymerase chain reaction. Seroprevalence of polyomavirus-specific antibodies was determined in 451 control subjects. MCPyV strain-specific antibody recognition was investigated by replacing coding sequences from MCPyV strain 350 with those from MCPyV strain w162.ResultsWe found that 36 (88%) of 41 patients with Merkel cell carcinoma carried antibodies against VP1 from MCPyV w162 compared with 40 (53%) of the 76 control subjects (odds ratio adjusted for age and sex = 6.6, 95% confidence interval [CI] = 2.3 to 18.8). MCPyV DNA was detectable in 24 (77%) of the 31 Merkel cell carcinoma tumors available, with 22 (92%) of these 24 patients also carrying antibodies against MCPyV. Among 451 control subjects from the general population, prevalence of antibodies against human polyomaviruses was 92% (95% CI = 89% to 94%) for BK virus, 45% (95% CI = 40% to 50%) for JC virus, 98% (95% CI = 96% to 99%) for WU polyomavirus, 90% (95% CI = 87% to 93%) for KI polyomavirus, and 59% (95% CI = 55% to 64%) for MCPyV. Few case patients had reactivity against MCPyV strain 350; however, indistinguishable reactivities were found with VP1 from strain 350 carrying a double mutation (residues 288 and 316) and VP1 from strain w162.ConclusionInfection with MCPyV is common in the general population. MCPyV, but not other human polyomaviruses, appears to be associated with Merkel cell carcinoma.

Dataset Information

Distinct merkel cell polyomavirus molecular features in tumour and non tumour specimens from patients with merkel cell carcinoma.

Publications

Distinct merkel cell polyomavirus molecular features in tumour and non tumour specimens from patients with merkel cell carcinoma.

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