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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Histogenesis of pure and combined Merkel cell carcinomas: An immunohistochemical study of 14 cases.
TL;DR: It is hypothesized that combined MCC undergo multidirectional differentiation into squamous, glandular, mesenchymal and Merkel cells, which originate from the hair follicle stem cells.
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Advances in Immunotherapy for Metastatic Merkel Cell Carcinoma: A Clinician's Guide
TL;DR: PD-1 axis checkpoint inhibitors are now regarded as the preferred frontline systemic therapy in eligible patients (including both VP- and VN-MCC), with impressive frequency, durability, and depth of objective responses, which compare favorably to those of most solid tumors.
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A "hit-and-run" affair - A possible link for cancer progression in virally driven cancers.
TL;DR: If the hit-and-run theory is true, viruses might cause more cancers than previously thought and will have implications in the prevention of many cancers through implementing vaccination programs.
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Contribution of Beta-HPV Infection and UV Damage to Rapid-Onset Cutaneous Squamous Cell Carcinoma during BRAF-Inhibition Therapy.
Daniel N. Cohen,Steven K. Lawson,Aaron C. Shaver,Liping Du,Harrison P. Nguyen,Qin He,Douglas B. Johnson,Wilfred A. Lumbang,Brent R. Moody,James L. Prescott,Pranil Chandra,Alan S. Boyd,Alan S. Boyd,Jeffrey P. Zwerner,Jeffrey P. Zwerner,Jason B. Robbins,Jason B. Robbins,Stephen K. Tyring,Peter L. Rady,James D. Chappell,Yu Shyr,Jeffrey R. Infante,Jeffrey A. Sosman +22 more
TL;DR: These findings enhance the understanding of factors cooperating with BRAF inhibition that accelerate keratinocyte oncogenesis as well as broaden the knowledge base of multifactorial mediators of cancer in general.
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PD-L1 inhibition with avelumab for metastatic Merkel cell carcinoma.
TL;DR: The JAVELIN Merkel 200 (NCT02155647) trial tested the use of avelumab, a human IgG1 monoclonal antibody against PD-L1, in metastatic MCC, and recently became the first approved drug for metastatics MCC.
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.