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
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Modulation of DNA Damage and Repair Pathways by Human Tumour Viruses
TL;DR: This review summarises the current literature regarding the complex relationship between known human tumour viruses and the DDR and aims to shed light on how these interactions can contribute to genomic instability and ultimately the development of human cancers.
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RB1 is the crucial target of the Merkel cell polyomavirus Large T antigen in Merkel cell carcinoma cells
Sonja Hesbacher,Lisa Pfitzer,Lisa Pfitzer,Katharina Wiedorfer,Sabrina Angermeyer,Andreas Borst,Sebastian Haferkamp,Claus-Jürgen Scholz,Marion Wobser,David Schrama,Roland Houben +10 more
TL;DR: The results suggest that RB1 is the dominant tumor suppressor PP in MCC, and that inactivation of RB1 by MCPyV-LT is largely sufficient for its growth supporting function in established MCPYV-positive MCC cells.
Journal ArticleDOI
From Stockholm to Malawi: recent developments in studying human polyomaviruses
Mariet C.W. Feltkamp,Siamaque Kazem,Els van der Meijden,Chris Lauber,Alexander E. Gorbalenya,Alexander E. Gorbalenya +5 more
TL;DR: This review summarizes the recent developments in studying the novel human polyomaviruses, and touches upon several aspects of polyomvirus virology, pathogenicity, epidemiology and phylogeny.
Journal ArticleDOI
Viruses and human cancer: From detection to causality
Ronit Sarid,Shou-Jiang Gao +1 more
TL;DR: It is anticipated that in the next few decades many additional human cancer viruses will be discovered and the mechanisms underlying viral oncogenesis delineated and it can be expected that better tools for preventing and treating virus-associated cancer will be available in the near future.
Journal ArticleDOI
Effect of host, tumor, diagnostic, and treatment variables on outcomes in a large cohort with merkel cell carcinoma
Maryam M. Asgari,Maryam M. Asgari,Monica Sokil,E. Margaret Warton,Jayasri G. Iyer,Kelly G. Paulson,Paul Nghiem,Paul Nghiem +7 more
TL;DR: Tumor site and extent, results of pathologic nodal evaluation, and the presence of radiation treatment were associated with MCC recurrence, whereas chemotherapy was not associated with any outcomes.
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