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

C. Martel-Jantin; C. Filippone; O. Cassar; M. Peter; G. Tomasic; P. Vielh; J. Brière; T. Petrella; M. H. Aubriot-Lorton; L. Mortier; G. Jouvion; X. Sastre-Garau; C. Robert; A. Gessain

doi:10.1016/j.virol.2012.01.018

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

C. Martel-Jantin, C. Filippone, O. Cassar, M. Peter, G. Tomasic, P. Vielh, J. Brière, T. Petrella, M. H. Aubriot-Lorton, L. Mortier, G. Jouvion, X. Sastre-Garau, C. Robert, A. Gessain

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Résumé

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.

langue originale	Anglais
Pages (de - à)	134-142
Nombre de pages	9
journal	Virology
Volume	426
Numéro de publication	2
Les DOIs	https://doi.org/10.1016/j.virol.2012.01.018
état	Publié - 10 mai 2012

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10.1016/j.virol.2012.01.018

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@article{b1ebe650f3124775abc561168a735ef1,

title = "Genetic variability and integration of Merkel cell polyomavirus in Merkel cell carcinoma",

abstract = "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.",

keywords = "Genetic variability, Merkel cell carcinoma, Merkel cell polyomavirus, Oncogenic viruses, Viral integration",

author = "C. Martel-Jantin and C. Filippone and O. Cassar and M. Peter and G. Tomasic and P. Vielh and J. Bri{\`e}re and T. Petrella and Aubriot-Lorton, {M. H.} and L. Mortier and G. Jouvion and X. Sastre-Garau and C. Robert and A. Gessain",

note = "Funding Information: We thank the Institut Pasteur , the Association pour la Recherche sur le Cancer ( A09/1/5041 , 2009) and La Ligue Nationale Contre le Cancer ( RS10/75-1 , 2010; RS11/75-63 ) for financial support. Claire Martel-Jantin was financially supported by the Minist{\`e}re de l'Enseignement Sup{\'e}rieur et de la Recherche (MESR) of France. Claudia Filippone was financially supported by the program “DIM Maladies Infectieuses Parasitaires et Nosocomiales Emergentes” from Ile-de-France , and from the European Program “EMPERIE”.",

year = "2012",

month = may,

day = "10",

doi = "10.1016/j.virol.2012.01.018",

language = "English",

volume = "426",

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T1 - Genetic variability and integration of Merkel cell polyomavirus in Merkel cell carcinoma

AU - Martel-Jantin, C.

AU - Filippone, C.

AU - Cassar, O.

AU - Peter, M.

AU - Tomasic, G.

AU - Vielh, P.

AU - Brière, J.

AU - Petrella, T.

AU - Aubriot-Lorton, M. H.

AU - Mortier, L.

AU - Jouvion, G.

AU - Sastre-Garau, X.

AU - Robert, C.

AU - Gessain, A.

N1 - Funding Information: We thank the Institut Pasteur , the Association pour la Recherche sur le Cancer ( A09/1/5041 , 2009) and La Ligue Nationale Contre le Cancer ( RS10/75-1 , 2010; RS11/75-63 ) for financial support. Claire Martel-Jantin was financially supported by the Ministère de l'Enseignement Supérieur et de la Recherche (MESR) of France. Claudia Filippone was financially supported by the program “DIM Maladies Infectieuses Parasitaires et Nosocomiales Emergentes” from Ile-de-France , and from the European Program “EMPERIE”.

PY - 2012/5/10

Y1 - 2012/5/10

N2 - 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.

AB - 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.

KW - Genetic variability

KW - Merkel cell carcinoma

KW - Merkel cell polyomavirus

KW - Oncogenic viruses

KW - Viral integration

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