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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Detection of Merkel cell polyomavirus (MCPyV) in Merkel cell carcinoma cell lines: cell morphology and growth phenotype do not reflect presence of the virus
TL;DR: A novel classification scheme based on MCPyV presence, integration patterns and T‐Ag mutations is suggested, indicating that the distinguishing features are either inherently independent of viral infection or have become so in the course of tumorigenesis and/or cell line establishment.
Journal ArticleDOI
Merkel cell carcinoma: An Australian perspective and the importance of addressing the regional lymph nodes in clinically node-negative patients
Julie Howle,Julie Howle,T. Michael Hughes,T. Michael Hughes,Val Gebski,Val Gebski,Val Gebski,Michael J. Veness,Michael J. Veness +8 more
TL;DR: A high rate of nodal relapse occurred in patients with stage I disease who had undergone treatment of the primary site only, and these patients may have benefited from sentinel lymph node biopsy and subsequenttreatment of the nodal basin if micrometastatic disease was present.
Journal ArticleDOI
Seroprevalence of human polyomavirus 9 and cross-reactivity to African green monkey-derived lymphotropic polyomavirus
TL;DR: The HPyV9 seroprevalence was determined, indicating that certain immunocompromised patient groups may be at a higher risk for primary infection with or for reactivation of HPYV9.
Journal ArticleDOI
Clinical and molecular characterization of virus-positive and virus-negative Merkel cell carcinoma.
Gabriel J. Starrett,Manisha Thakuria,Manisha Thakuria,Tianqi Chen,Christina Marcelus,Jingwei Cheng,Jingwei Cheng,Jason Nomburg,Aaron R. Thorner,Michael K. Slevin,Winslow Powers,Robert Burns,Caitlin E Perry,Adriano Piris,Frank C. Kuo,Guilherme Rabinowits,Guilherme Rabinowits,Anita Giobbie-Hurder,Laura E. MacConaill,Laura E. MacConaill,James A. DeCaprio,James A. DeCaprio,James A. DeCaprio +22 more
TL;DR: The value of high-confidence virus detection for identifying molecular mechanisms of UV and viral oncogenesis in MCC is demonstrated and a surprising association of immunosuppression with virus-negative MCC and significantly shortened overall survival is revealed.
Journal ArticleDOI
Retinoblastoma gene mutations detected by whole exome sequencing of Merkel cell carcinoma.
Patrick J. Cimino,Diane Robirds,Sheryl R. Tripp,John D. Pfeifer,Haley J. Abel,Eric J. Duncavage +5 more
TL;DR: This novel finding suggests that the retinoblastoma pathway dysregulation leads to an overlapping Merkel cell carcinoma phenotype and that oncogenesis occurs through either a polyomavirus-dependent (viral large T antigen expression) or polyomvirus-independent (host somatic mutation) mechanism.
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