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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High Levels of Antibodies Against Merkel Cell Polyomavirus Identify a Subset of Patients With Merkel Cell Carcinoma With Better Clinical Outcome
Antoine Touzé,Emmanuelle Le Bidre,Hélène Laude,Maxime Fleury,Raphaël Cazal,Françoise Arnold,Agnès Carlotti,Eve Maubec,François Aubin,Marie-Françoise Avril,Flore Rozenberg,Mauro Tognon,Annabel Maruani,Serge Guyétant,Gérard Lorette,Pierre Coursaget +15 more
TL;DR: High titers of MCV antibodies in a much higher proportion of patients with MCC than in controls confirmed the association between MCV infection and MCC and suggested that there are at least two distinct etiologic causes of MCC.
Journal ArticleDOI
Virus identification in unknown tropical febrile illness cases using deep sequencing.
Nathan L. Yozwiak,Peter Skewes-Cox,Mark D. Stenglein,Angel Balmaseda,Eva Harris,Joseph L. DeRisi +5 more
TL;DR: The utility of unbiased metagenomic approaches in the detection of known and divergent viruses in the study of tropical febrile illness is demonstrated.
Journal ArticleDOI
Association of Merkel cell polyomavirus infection with clinicopathological differences in Merkel cell carcinoma
Hiromi Higaki-Mori,Satoshi Kuwamoto,Takeshi Iwasaki,Masako Kato,Ichiro Murakami,Keiko Nagata,Hitoshi Sano,Yasushi Horie,Yuichi Yoshida,Osamu Yamamoto,Kaori Adachi,Eiji Nanba,Kazuhiko Hayashi +12 more
TL;DR: The results suggest that Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas likely develop through different tumorigenic pathways and that the presence or absence of Merkelcell polyomvirus in the tumor is still an important factor that affects survival in patients with Merkel cell cancer.
Journal ArticleDOI
VirusSeq: software to identify viruses and their integration sites using next-generation sequencing of human cancer tissue
TL;DR: A new algorithmic method, VirusSeq, that accurately detects the known viruses and their integration sites in the human genome using next-generation sequencing data and can also perform this function using whole-genome sequencing data of human tissue.
Journal ArticleDOI
Glycosaminoglycans and Sialylated Glycans Sequentially Facilitate Merkel Cell Polyomavirus Infectious Entry
TL;DR: The findings suggest a model in which MCV infectious entry occurs via initial cell binding mediated primarily by HS, followed by secondary interactions with a sialylated entry co-factor, and the development of inhibitors of MCV infection is facilitated.
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