Genetic variability and integration of Merkel cell polyomavirus in Merkel cell carcinoma

被引:72
作者
Martel-Jantin, C.
Filippone, C.
Cassar, O.
Peter, M. [2 ]
Tomasic, G. [4 ]
Vielh, P. [3 ]
Briere, J. [5 ]
Petrella, T. [6 ]
Aubriot-Lorton, M. H. [7 ]
Mortier, L. [8 ]
Jouvion, G. [9 ]
Sastre-Garau, X. [2 ]
Robert, C. [4 ]
Gessain, A. [1 ]
机构
[1] Inst Pasteur, CNRS, Dept Virol,URA 3015, Unite Epidemiol & Physiopathol Virus Oncogens, F-75724 Paris, France
[2] Inst Curie, Dept Pathol, Paris, France
[3] Inst Gustave Roussy, Lab Rech Translat, Villejuif, France
[4] Inst Gustave Roussy, Serv Dermatol & Anatomopathol, Villejuif, France
[5] Hop St Louis, Lab Anatomopathol, Paris, France
[6] Ctr Pathol Dijon, Dijon, France
[7] CHU Dijon, Serv Anat & Cytol Pathol, Dijon, France
[8] CHU Lille, Serv Dermatol, Lille, France
[9] Inst Pasteur, Unite Histopathol Humaine & Modeles Animaux, F-75724 Paris, France
关键词
Merkel cell polyomavirus; Viral integration; Oncogenic viruses; Genetic variability; Merkel cell carcinoma; LARGE T-ANTIGEN; RESPIRATORY-TRACT; TRANSFORMED RAT; JC VIRUS; DNA; INFECTION; SEQUENCES; ANTIBODIES; TISSUES; DELETION;
D O I
10.1016/j.virol.2012.01.018
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Merkel cell polyomavirus (MCPyV) is associated to Merkel cell carcinoma (MCC). We studied 113 MCC tumoral skin lesions originating from 97 patients. MCPyV detection was higher in fresh-frozen (FF) biopsies (94%) than in formalin-fixed paraffin-embedded biopsies (39-47%). Mean viral load in FF tumor was of 7.5 copies per cell with a very wide range (0.01-95.4). Nineteen complete sequences of LTAg were obtained, mainly from FF biopsies when the viral load was high. Seventeen showed stop codons, all localized downstream of the pRb protein binding domain. Sequence comparison and phylogenetic analysis showed that all sequences clustered in the large C clade of MCPyV strains. MCPyV integration was demonstrated in 19 out of 27 FF MCC DNA biopsies without evidence of specific host cellular genome integration site. In 13/19 cases, the viral junction was located within the second exon of the LTAg, after the pRB binding domain. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:134 / 142
页数:9
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