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
More filters
Journal ArticleDOI
CD8+ lymphocyte intratumoral infiltration as a stage-independent predictor of Merkel cell carcinoma survival: a population-based study.
Kelly G. Paulson,Jayasri G. Iyer,William T. Simonson,Astrid Blom,Renee Thibodeau,Miranda Schmidt,Stephanie Pietromonaco,Monica Sokil,E. Margaret Warton,Maryam M. Asgari,Paul Nghiem,Paul Nghiem +11 more
TL;DR: This study of prospectively captured MCC cases supports the concept that cellular immunity is important in MCC outcome and that CD8+ lymphocyte infiltration adds prognostic information to conventional staging and that IT-CD8s predict survival among a population-based MCC cohort.
Journal ArticleDOI
Merkel cell polyomavirus recruits MYCL to the EP400 complex to promote oncogenesis
Jingwei Cheng,Donglim Esther Park,Christian Berrios,Elizabeth A. White,Reety Arora,Rosa Yoon,Timothy Branigan,Tengfei Xiao,Thomas Westerling,Thomas Westerling,Alexander J. Federation,Rhamy Zeid,Benjamin J. Strober,Selene K. Swanson,Laurence Florens,James E. Bradner,James E. Bradner,Myles Brown,Peter M. Howley,Megha Padi,Michael P. Washburn,Michael P. Washburn,James A. DeCaprio,James A. DeCaprio +23 more
TL;DR: It is demonstrated that ST can activate gene expression in a EP400 and MYCL dependent manner and this activity contributes to cellular transformation and generation of induced pluripotent stem cells.
Journal ArticleDOI
The prevention of infection-associated cancers
Silvio De Flora,Paolo Bonanni +1 more
TL;DR: The present article reviews the microbial and parasitic diseases that have been associated so far with human cancers, draws an overview of their burden in cancer epidemiology, deals with applicable prevention strategies and provides examples of co-ordinated approaches to the control of cancers associated with HBV, HCV, HPV, human immunodeficiency virus and H.pylori infections.
Journal ArticleDOI
Merkel cell polyomavirus infection occurs during early childhood and is transmitted between siblings.
Claire Martel-Jantin,Claire Martel-Jantin,Claire Martel-Jantin,Vincent Pedergnana,Vincent Pedergnana,Jérôme T. J. Nicol,Valérie Leblond,David-Alexandre Trégouët,Patricia Tortevoye,Patricia Tortevoye,Sabine Plancoulaine,P. Coursaget,Antoine Touzé,Laurent Abel,Laurent Abel,Laurent Abel,Antoine Gessain,Antoine Gessain +17 more
TL;DR: The results suggest that MCPyV infection is acquired through close contact, possibly involving saliva and/or the skin, especially between young siblings and between mothers and their children.
Journal ArticleDOI
Bromodomain Protein Brd4 Plays a Key Role in Merkel Cell Polyomavirus DNA Replication
TL;DR: It is demonstrated that bromodomain protein 4 (Brd4) interacts with MCV large T antigen (LT) and plays a critical role in viral DNA replication and obstructing the physiologic interaction between Brd4 and host chromatin with the chemical compound JQ1(+) leads to enhanced MCV DNA replication.
References
More filters
Journal ArticleDOI
Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma
Yuan Chang,Ethel Cesarman,Melissa S. Pessin,Frank Lee,Janice Culpepper,Daniel M. Knowles,Patrick S. Moore +6 more
TL;DR: unique sequences present in more than 90 percent of Kaposi's sarcoma tissues obtained from patients with acquired immunodeficiency syndrome (AIDS) appear to define a new human herpesvirus.
Journal ArticleDOI
A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions.
TL;DR: The data indicate that HPV 16 DNA prevails in malignant tumors, rendering an accidental contamination with papillomavirus DNA from adjacent papillomas rather unlikely, and suggests a dependence of HPV 16 replication on helper virus.
Journal ArticleDOI
SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene
James A. DeCaprio,John W. Ludlow,James Figge,Jin-Yuh Shew,Chun-Ming Huang,Wen-Hwa Lee,Erika Marsilio,Eva Paucha,David M. Livingston +8 more
TL;DR: Results are consistent with a model for transformation by SV40 which, at least in part, involves T/p110-114 complex formation and the perturbation of Rb protein and/or T function.
Journal ArticleDOI
Identification of a novel polyomavirus from patients with acute respiratory tract infections.
Anne M. Gaynor,Michael D. Nissen,David M. Whiley,Ian M. Mackay,Stephen B. Lambert,Guang Wu,Daniel C. Brennan,Gregory A. Storch,Theo P. Sloots,David Wang +9 more
TL;DR: The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen.
Journal ArticleDOI
Identification of a Third Human Polyomavirus
Tobias Allander,Kalle Andreasson,Shawon Gupta,Annelie Bjerkner,Gordana Bogdanovic,Mats A. A. Persson,Tina Dalianis,Torbjörn Ramqvist,Björn Andersson +8 more
TL;DR: The identification of a previously unknown polyomvirus provisionally named KI polyomavirus, which is phylogenetically related to other primatepolyomaviruses in the early region of the genome but has very little homology to known polyomVirus in the late region, illustrates how unbiased screening of respiratory tract samples can be used for the discovery of diverse virus types.