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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Tumor-Infiltrating Merkel Cell Polyomavirus-Specific T Cells Are Diverse and Associated with Improved Patient Survival.
Natalie J. Miller,Candice D. Church,Lichun Dong,David A. Crispin,Matthew Fitzgibbon,K. Lachance,Lichen Jing,Michi M. Shinohara,Ioannis Gavvovidis,Gerald Willimsky,Martin W. McIntosh,Thomas Blankenstein,Thomas Blankenstein,David M. Koelle,David M. Koelle,Paul Nghiem +15 more
TL;DR: Intratumoral infiltration by MCPyV-specific T cells was associated with significantly improved MCC-specific survival, suggesting that augmenting the number or avidity of virus- specific T cells may have therapeutic benefit.
Journal ArticleDOI
Merkel Cell Carcinoma in the Age of Immunotherapy: Facts and Hopes.
TL;DR: Recent progress in MCC is highlighted including the underlying mechanisms of immune evasion and emerging approaches to augment the efficacy of PD-1 pathway blockade, including the first-ever FDA drug approval for this disease.
Journal ArticleDOI
Entry tropism of BK and Merkel cell polyomaviruses in cell culture.
TL;DR: Application of native MCV virions to a subset of highly transducible cell types suggested that the lines do not support robust replication of MCV, consistent with recent proposals that the MCV late phase may be governed by cellular differentiation in vivo.
Journal ArticleDOI
Identification of epidermal progenitors for the Merkel cell lineage
TL;DR: A previously undescribed population of epidermal progenitors that reside in the touch domes of hairy skin, termed touch dome progenitor cells (TDPCs) are identified and possess a unique transcript profile that appears to be enforced by the juxtaposition of TDPCs with Merkel cells within the touch dome niche.
Journal ArticleDOI
A Practical Update of Surgical Management of Merkel Cell Carcinoma of the Skin
TL;DR: The role of surgeons in the treatment of Merkel cell carcinoma of the skin is reviewed, with respect to diagnosis and treatment, and data are insufficient to assess whether adjuvant chemotherapy improves survival.
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