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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The biology and treatment of Merkel cell carcinoma: current understanding and research priorities
Paul W. Harms,Kelly L. Harms,Patrick S. Moore,James A. DeCaprio,Paul Nghiem,Michael K K Wong,Isaac Brownell +6 more
TL;DR: The availability of immune checkpoint inhibition has improved the outcomes of a subset of patients with MCC, although many unmet needs continue to exist, according to this Consensus Statement.
Journal ArticleDOI
Taxonomical developments in the family Polyomaviridae
Reimar Johne,Christopher B. Buck,Tobias Allander,Walter J. Atwood,Robert L. Garcea,Michael J. Imperiale,Eugene O. Major,Torbjörn Ramqvist,Leonard C. Norkin +8 more
TL;DR: The Polyomaviridae Study Group of the International Committee on Taxonomy of Viruses (ICTV) has recommended several taxonomical revisions, as follows: the family Polyomviridae, which is currently constituted as a single genus, will be comprised of three genera: two containing mammalian viruses and one containing avian viruses.
Journal ArticleDOI
Merkel Cell Carcinoma: Incidence, Mortality, and Risk of Other Cancers
Jeanette Kaae,Anne Vinkel Hansen,Robert J. Biggar,Heather A. Boyd,Patrick S. Moore,Jan Wohlfahrt,Mads Melbye +6 more
TL;DR: H Heightened awareness of the association between MCC and other cancers, particularly squamous cell carcinoma and chronic lymphocytic leukemia, may facilitate earlier clinical detection and treatment of MCC, thereby improving patient survival.
Journal ArticleDOI
Viral pathogen discovery.
TL;DR: Genomic approaches for pathogen discovery, including consensus polymerase chain reaction (PCR), microarrays, and unbiased next-generation sequencing (NGS), have the capacity to comprehensively identify novel microbes present in clinical samples and are successful in rapidly identifying emerging outbreak threats.
Journal ArticleDOI
Identification of MW Polyomavirus, a Novel Polyomavirus in Human Stool
Erica A. Siebrasse,Alejandro Reyes,Efrem S. Lim,Guoyan Zhao,Rajhab S. Mkakosya,Mark J. Manary,Jeffrey I. Gordon,David Wang +7 more
TL;DR: A novel polyomavirus present in multiple human stool samples and predicted to encode the large T antigen and small T antigen early proteins and the VP1, VP2, and VP3 structural proteins is discovered.
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