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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The common mechanisms of transformation by the small DNA tumor viruses: The inactivation of tumor suppressor gene products: p53.
TL;DR: Both the p53 tumor suppressor gene, which was uncovered in the studies with these viruses, and the retinoblastoma protein, have been shown to play a central role in the origins of human cancers via both somatic and germ line mutations in those genes.
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Genetics of pigmentation in skin cancer--a review.
Dominique Scherer,Rajesh Kumar +1 more
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A novel rhabdovirus associated with acute hemorrhagic fever in central Africa.
Gilda Grard,Joseph N. Fair,Deanna Lee,Elizabeth Slikas,Imke Steffen,Jean-Jacques Muyembe,Taylor Sittler,Narayanan Veeraraghavan,J. Graham Ruby,J. Graham Ruby,Chunlin Wang,Maria Makuwa,Prime Mulembakani,Robert B. Tesh,Jonna A. K. Mazet,Anne W. Rimoin,Travis Taylor,Bradley S. Schneider,Graham Simmons,Eric Delwart,Nathan D. Wolfe,Charles Y. Chiu,Eric M. Leroy +22 more
TL;DR: Deep sequencing was used to discover a novel rhabdovirus (Bas-Congo virus, or BASV) associated with a 2009 outbreak of 3 human cases of acute hemorrhagic fever in Mangala village, Democratic Republic of Congo, Africa, and revealed that BASV is highly divergent and shares less than 34% amino acid identity with any other rhabDovirus.
Journal ArticleDOI
Response rates and durability of chemotherapy among 62 patients with metastatic Merkel cell carcinoma
Jayasri G. Iyer,Astrid Blom,Ryan Doumani,C. Lewis,Erica S. Tarabadkar,Austin Anderson,Christine Ma,Amy Bestick,Upendra Parvathaneni,Shailender Bhatia,Paul Nghiem +10 more
TL;DR: First‐line chemotherapy is associated with a high RR in metastatic MCC, but responses are typically not durable, and the median PFS is only 3 months, which suggests rapid emergence of chemoresistance in MCC tumors.
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