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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Merkel Polyomavirus-Specific T Cells Fluctuate with Merkel Cell Carcinoma Burden and Express Therapeutically Targetable PD-1 and Tim-3 Exhaustion Markers
Olga K. Afanasiev,Lola Yelistratova,Miller Natalie J,Kotaro Nagase,Kelly G. Paulson,Jayasri G. Iyer,Dafina Ibrani,David M. Koelle,Paul Nghiem +8 more
TL;DR: MCC-targeting T cells expand with tumor burden and express high levels of immune checkpoint receptors PD-1 and Tim-3, and reversal of these inhibitory pathways is therefore a promising therapeutic approach for this virus-driven cancer.
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Acquired cancer resistance to combination immunotherapy from transcriptional loss of class I HLA
Kelly G. Paulson,Kelly G. Paulson,Kelly G. Paulson,Valentin Voillet,Megan S. McAfee,Daniel Hunter,Felecia Wagener,M. Perdicchio,M. Perdicchio,William J. Valente,Samson J. Koelle,Samson J. Koelle,Candice D. Church,Natalie Vandeven,Holly N. Thomas,Aric Colunga,Jayasri G. Iyer,Cassian Yee,Rima M. Kulikauskas,David M. Koelle,David M. Koelle,David M. Koelle,Robert H. Pierce,Jason H. Bielas,Jason H. Bielas,Phil Greenberg,Phil Greenberg,Shailender Bhatia,Shailender Bhatia,Shailender Bhatia,Raphael Gottardo,Raphael Gottardo,Paul Nghiem,Paul Nghiem,Paul Nghiem,Aude G. Chapuis,Aude G. Chapuis,Aude G. Chapuis +37 more
TL;DR: Single cell RNA sequencing identified dynamic transcriptional suppression of the specific HLA genes presenting the targeted viral epitope in the resistant tumor as a consequence of intense CD8-mediated immunologic pressure and identified a novel mechanism of acquired, gene-specific transcriptional suppressed of HLAs.
Journal ArticleDOI
Merkel Cell Carcinoma: A Virus-Induced Human Cancer
Yuan Chang,Patrick S. Moore +1 more
TL;DR: This human cancer virus provides a new model in which a common, mostly harmless member of the human viral flora can initiate cancer if it acquires a precise set of mutations in a host with specific susceptibility factors, such as age and immune suppression.
Journal ArticleDOI
Discovery of STL polyomavirus, a polyomavirus of ancestral recombinant origin that encodes a unique T antigen by alternative splicing
Efrem S. Lim,Alejandro Reyes,Martin Antonio,Debasish Saha,Usman N. Ikumapayi,Mitchell Adeyemi,O. Colin Stine,Rebecca Skelton,Daniel C. Brennan,Rajhab S. Mkakosya,Mark J. Manary,Mark J. Manary,Jeffrey I. Gordon,David Wang +13 more
TL;DR: A novel polyomavirus recovered from the fecal microbiota of a child in Malawi is described, provisionally named STLPyV, which has a mosaic genome and shares an ancestral recombinant origin with MWPyV.
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Microbes and Cancer
Amiran Dzutsev,Jonathan H. Badger,Ernesto Perez-Chanona,Soumen Roy,Rosalba Salcedo,Carolyne K. Smith,Giorgio Trinchieri +6 more
TL;DR: The mechanisms underlying the interaction of the microbiota with cancer and the evidence suggesting that the microbiota could be targeted to improve therapy while attenuating adverse reactions are reviewed.
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.