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

Claire Martel-Jantin (1) , Claudia Filippone (1) , Olivier Cassar (1) , M Peter (2) , Gorana Tomasic (3, 4) , Philippe Vielh (5) , Josette Brière (6) , Tony Petrella (7) , Marie-Hélène Aubriot-Lorton (8) , Laurent Mortier (9) , Grégory Jouvion (10) , Xavier Sastre-Garau (2) , Caroline Robert (11) , Antoine Gessain (1)

1 EPVO (UMR_3569 / U-Pasteur_3) - Epidémiologie et Physiopathologie des Virus Oncogènes
2 Institut Curie [Paris]
3 Département de biologie et pathologie médicales [Gustave Roussy]
4 IGR - Institut Gustave Roussy
5 Laboratoire de recherche translationnelle
6 Service d'anatomo-pathologie [Paris]
7 Centre de pathologie [Dijon]
8 Service d'anatomie et de cytologie pathologiques
9 Service de dermatologie
10 Histopathologie humaine et Modèles animaux
11 Service de dermatologie

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.

Domains: Life Sciences [q-bio]

Claire Martel-Jantin, Claudia Filippone, Olivier Cassar, M Peter, Gorana Tomasic, et al.. Genetic variability and integration of Merkel cell polyomavirus in Merkel cell carcinoma.. Virology, 2012, 426 (2), pp.134-42. ⟨10.1016/j.virol.2012.01.018⟩. ⟨pasteur-01370953⟩