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 Epidemiology of Cancers in Human Immunodeficiency Virus Infection and After Organ Transplantation
TL;DR: An update on the association between immune deficiency and cancer risk in people with human immunodeficiency virus (HIV) and in solid organ transplant recipients is provided and it is not clear whether reduction of immune deficiency reduces cancer risk.
Journal ArticleDOI
Different serologic behavior of MCPyV, TSPyV, HPyV6, HPyV7 and HPyV9 polyomaviruses found on the skin.
Els van der Meijden,Seweryn Bialasiewicz,Seweryn Bialasiewicz,R. Rockett,R. Rockett,Sarah Tozer,Sarah Tozer,Theo P. Sloots,Theo P. Sloots,Mariet C.W. Feltkamp +9 more
TL;DR: Based on the identified serologic profiles, MCPyV seems to cluster withHPyV6 and HPyV7, and TSPyV and HPs9 by themselves, which indicate heterogeneity among cutaneous polyomaviruses and probably reflect differences in exposure and pathogenic behavior of these viruses.
Journal ArticleDOI
Activation of PI3K signaling in Merkel cell carcinoma
Valentina Nardi,Youngchul Song,Juan A. Santamaria-Barria,Arjola K. Cosper,Quynh Lam,Anthony C. Faber,Genevieve M. Boland,Beow Y. Yeap,Kristin Bergethon,Vanessa L. Scialabba,Hensin Tsao,Jeffrey Settleman,David P. Ryan,Darrell R. Borger,Atul K. Bhan,Mai P. Hoang,Anthony J. Iafrate,James C. Cusack,Jeffrey A. Engelman,Dora Dias-Santagata +19 more
TL;DR: PI3K pathway activation may drive tumorigenesis in a subset of MCC and screening these tumors for PIK3CA mutations could help identify patients who may respond to treatment with PI3K pathways inhibitors, under active clinical development.
Journal ArticleDOI
Viral Oncogenes, Noncoding RNAs, and RNA Splicing in Human Tumor Viruses
TL;DR: Among the determined viral microRNA precursors, EBV encode 25 from two major clusters (BART and BHRF1), KSHV encodes 12 from a latent region, human polyomavirus MCV produce only one microRNA from the late region antisense to early transcripts, but HPVs appears to produce no viral microRNAs.
Journal ArticleDOI
Merkel Cell Polyomavirus Large T Antigen Disrupts Host Genomic Integrity and Inhibits Cellular Proliferation
TL;DR: It is demonstrated that MCV LT-induced DDR activates p53 pathway, leading to the inhibition of cellular proliferation, and a key difference between MCVLT and simian vacuolating virus 40 LT is revealed, which activates a DDR but inhibits p53 function.
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