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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Mutational landscape of MCPyV-positive and MCPyV-negative Merkel cell carcinomas with implications for immunotherapy.
Gerald Goh,Gerald Goh,Trent Walradt,Vladimir Markarov,Astrid Blom,Nadeem Riaz,Nadeem Riaz,Ryan Doumani,Krista Stafstrom,Ata S. Moshiri,Lola Yelistratova,Jonathan L. Levinsohn,Timothy A. Chan,Paul Nghiem,Paul Nghiem,Richard P. Lifton,Richard P. Lifton,Jaehyuk Choi,Jaehyuk Choi,Jaehyuk Choi +19 more
TL;DR: It is found that virus-negative MCCs harbor more tumor neoantigens than melanomas or non-small cell lung cancers (median of 173, 65, and 111 neoantIGens/sample, respectively), two cancers for which immune checkpoint blockade can produce durable clinical responses.
Journal ArticleDOI
A cornucopia of human polyomaviruses
TL;DR: The similarities and differences among the new human polyomaviruses are described and how these viruses might interact with their human host are discussed.
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Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008--a Swedish population-based study.
Britta Krynitz,Gustaf Edgren,Bernt Lindelöf,Eva Baecklund,C Brattström,Henryk E. Wilczek,Karin E. Smedby +6 more
TL;DR: Post‐transplant cancer risk varied by transplanted organ and by cancer site, with the bulk of the excess risk driven by an exceptionally high and accelerating risk of SCC.
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Clinical Factors Associated With Merkel Cell Polyomavirus Infection in Merkel Cell Carcinoma
TL;DR: Findings lend support to the hypothesis that viral infection is frequently associated with the pathogenesis of Merkel cell carcinoma.
Journal ArticleDOI
Merkel cell carcinoma: Epidemiology, prognosis, therapy and unmet medical needs.
Dirk Schadendorf,Céleste Lebbé,Axel zur Hausen,M.-F. Avril,Subramanian Hariharan,Murtuza Bharmal,Juergen C. Becker +6 more
TL;DR: Patients with advanced disease are encouraged to participate in clinical trials for treatment, indicating the largely unmet need for durable, safe treatment within this population.
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