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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Reviewing the current evidence supporting early B-cells as the cellular origin of Merkel cell carcinoma
Christopher Martin Sauer,Anke Haugg,Emil Chteinberg,Dorit Rennspiess,Véronique Winnepenninckx,Ernst J. M. Speel,Jürgen C. Becker,Anna Kordelia Kurz,A. zur Hausen +8 more
TL;DR: The recently formulated hypothesis of MCC originating from early B-cells is based on morphology, the consistent expression ofEarly B-cell lineage markers and the finding of clonal immunoglobulin chain rearrangement in MCC cells.
Journal ArticleDOI
Merkel cell carcinoma and Merkel cell polyomavirus: a systematic review and meta-analysis.
Jorge Santos-Juanes,Iván Fernández-Vega,N. Fuentes,Cristina Galache,Pablo Coto-Segura,Blanca Vivanco,Aurora Astudillo,Pablo Martínez-Camblor +7 more
TL;DR: The findings support the association between Merkel cell carcinoma and Merkel cell polyomavirus, however, a non‐negligible percentage of positive results have been identified in controls.
Journal ArticleDOI
Vascular E-Selectin Expression Correlates with CD8 Lymphocyte Infiltration and Improved Outcome in Merkel Cell Carcinoma
Olga K. Afanasiev,Kotaro Nagase,William T. Simonson,Natalie Vandeven,Astrid Blom,David M. Koelle,Rachael A. Clark,Paul Nghiem,Paul Nghiem +8 more
TL;DR: Data suggest that one mechanism of immune evasion in MCC may be restriction of T cell entry into the tumor, and existing therapeutic agents that modulate E-selectin expression and/or RNS generation may restore T cellEntry and could potentially synergize with other immune-stimulating therapies.
Journal ArticleDOI
Immunotherapy for skin cancer.
Kelly G. Paulson,Kelly G. Paulson,Miranda C. Lahman,Miranda C. Lahman,Aude G. Chapuis,Aude G. Chapuis,Isaac Brownell +6 more
TL;DR: This review will focus on the exciting progress with immunotherapy for skin cancers to date, and also the current understanding of the mechanisms of resistance to immunotherapy.
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Role of leucine-rich pentatricopeptide repeat motif-containing protein (LRPPRC) for anti-apoptosis and tumourigenesis in cancers
Tian Tian,Jun-ichiro Ikeda,Yi Wang,Suhana Mamat,Suhana Mamat,Wen-Juan Luo,Wen-Juan Luo,Katsuyuki Aozasa,Eiichi Morii +8 more
TL;DR: Findings indicate that LRPPRC played an important role in tumourigenesis through the resistance to apoptosis and high invasive activity.
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