Clonal integration of a polyomavirus in human Merkel cell carcinoma.
TLDR
In six of eight MCV-positive MCCs, viral DNA was integrated within the tumor genome in a clonal pattern, suggesting that MCV infection and integration preceded clonal expansion of the tumor cells, and MCV may be a contributing factor in the pathogenesis of MCC.Abstract:
Merkel cell carcinoma (MCC) is a rare but aggressive human skin cancer that typically affects elderly and immunosuppressed individuals, a feature suggestive of an infectious origin. We studied MCC samples by digital transcriptome subtraction and detected a fusion transcript between a previously undescribed virus T antigen and a human receptor tyrosine phosphatase. Further investigation led to identification and sequence analysis of the 5387-base-pair genome of a previously unknown polyomavirus that we call Merkel cell polyomavirus (MCV or MCPyV). MCV sequences were detected in 8 of 10 (80%) MCC tumors but only 5 of 59 (8%) control tissues from various body sites and 4 of 25 (16%) control skin tissues. In six of eight MCV-positive MCCs, viral DNA was integrated within the tumor genome in a clonal pattern, suggesting that MCV infection and integration preceded clonal expansion of the tumor cells. Thus, MCV may be a contributing factor in the pathogenesis of MCC.read more
Citations
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Metagenomics for the discovery of novel human viruses.
Patrick Tang,Charles Y. Chiu +1 more
TL;DR: Metagenomics-based tools, such as microarrays and high-throughput sequencing, have the potential to detect the full spectrum of viruses, including those present in low numbers.
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Early B-Cell Differentiation in Merkel Cell Carcinomas: Clues to Cellular Ancestry
Axel zur Hausen,Dorit Rennspiess,Véronique Winnepenninckx,Ernst-Jan M. Speel,Anna Kordelia Kurz +4 more
TL;DR: It is proposed that the cell of origin of MCCs is a pro/pre- or pre-B cell rather than the postmitotic Merkel cells, likely to induce the expression of simple cytokeratins as has been shown for SV40 in other nonepithelial cells.
Journal ArticleDOI
Chronic lymphocytic leukaemia patients have a high risk of Merkel-cell polyomavirus DNA-positive Merkel-cell carcinoma.
Virve Koljonen,Heli Kukko,Eero Pukkala,Risto Sankila,Tom Böhling,Erkki Tukiainen,Harri Sihto,Heikki Joensuu +7 more
TL;DR: It is concluded that patients diagnosed with CLL have a substantially increased risk for MCC, and vice versa, and Merkel-cell polyomavirus DNA is frequently present in MCCs that occur in CLL patients.
Journal ArticleDOI
Cell polarity proteins: common targets for tumorigenic human viruses.
TL;DR: Evidence is discussed supporting the hypothesis that human tumor viruses should serve as powerful tools for deciphering mechanisms whereby disruption of cell junctions and loss of cell polarity contribute to the development of many human cancers.
Journal ArticleDOI
Human polyoma viruses and disease with emphasis on clinical BK and JC.
TL;DR: Recently WU, KI and Merkel cell polyoma viruses have been isolated from humans and the exact role of these three newly discovered viruses in human disease is not known.
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