Merkel cell carcinoma; VP1; polyomavirus; replication; trichoblastoma; Pathology and Forensic Medicine; Histology; General Medicine
Abstract :
[en] [en] AIMS: Merkel cell carcinoma (MCC) is frequently caused by the Merkel cell polyomavirus (MCPyV). Characteristic for these virus-positive (VP) MCC is MCPyV integration into the host genome and truncation of the viral oncogene Large T antigen (LT), with full-length LT expression considered as incompatible with MCC growth. Genetic analysis of a VP-MCC/trichoblastoma combined tumour demonstrated that virus-driven MCC can arise from an epithelial cell. Here we describe two further cases of VP-MCC combined with an adnexal tumour, i.e. one trichoblastoma and one poroma.
METHODS AND RESULTS: Whole-genome sequencing of MCC/trichoblastoma again provided evidence of a trichoblastoma-derived MCC. Although an MCC-typical LT-truncating mutation was detected, we could not determine an integration site and we additionally detected a wildtype sequence encoding full-length LT. Similarly, Sanger sequencing of the combined MCC/poroma revealed coding sequences for both truncated and full-length LT. Moreover, in situ RNA hybridization demonstrated expression of a late region mRNA encoding the viral capsid protein VP1 in both combined as well as in a few cases of pure MCC.
CONCLUSION: The data presented here suggest the presence of wildtype MCPyV genomes and VP1 transcription in a subset of MCC.
Disciplines :
Oncology
Author, co-author :
Kervarrec, Thibault ; Department of Pathology, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France ; "Biologie des Infections à Polyomavirus" Team, UMR INRAE ISP 1282, Université de Tours, Tours, France
Appenzeller, Silke; Comprehensive Cancer Center Mainfranken, University Hospital of Würzburg, Würzburg, Germany
Tallet, Anne; Platform of Somatic Tumor Molecular Genetics, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France
Jullie, Marie-Laure; Department of Pathology, Hôpital Haut-Lévêque, CHU de Bordeaux, CARADERM Network, Pessac, France
Sohier, Pierre; Faculté de Médecine, Université Paris Cité, Paris, France ; Department of Pathology, Hôpital Cochin, AP-HP.Centre-Université Paris Cité, Paris, France
Guillonneau, Francois; 3P5 Proteomics, Hôpital Cochin, AP-HP, Centre-Université Paris Cité, Paris, France
Berthon, Patricia; "Biologie des Infections à Polyomavirus" Team, UMR INRAE ISP 1282, Université de Tours, Tours, France
Le Corre, Yannick; Dermatology Department, LUNAM Université, CHU Angers, Angers, France
Hainaut-Wierzbicka, Ewa; Dermatology Department, Université de Poitiers, CHU de Poitiers, Poitiers, France
Blom, Astrid; Department of General and Oncologic Dermatology, CARADERM Network Ambroise-Paré hospital, APHP & Research Unit EA 4340, University of Versailles-Saint-Quentin-en-Yvelines, Paris-Saclay University, Boulogne-Billancourt, France
Beneton, Nathalie; Dermatology Department, CHR Le Mans, Le Mans, France
Bens, Guido; Dermatology Department, CHR d'Orléans, Orléans, France ; Dermatology Department, CH de Blois, Blois, France
Nardin, Charline; Dermatology Department, Inserm 1098, Université de Franche Comté, CHU Besançon, Besançon, France
Aubin, Francois; Dermatology Department, Inserm 1098, Université de Franche Comté, CHU Besançon, Besançon, France
Dinulescu, Monica; Dermatology Department, CHR Rennes, Rennes, France ; Institut Dermatologique du Grand Ouest (IDGO), Rennes, France
Visée, Sebastien; Department of Pathology, Centre Hospitalier d'Angoulème, Angoulème, France
Herfs, Michael ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Touzé, Antoine; "Biologie des Infections à Polyomavirus" Team, UMR INRAE ISP 1282, Université de Tours, Tours, France
Guyétant, Serge; Department of Pathology, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France ; "Biologie des Infections à Polyomavirus" Team, UMR INRAE ISP 1282, Université de Tours, Tours, France
Samimi, Mahtab; "Biologie des Infections à Polyomavirus" Team, UMR INRAE ISP 1282, Université de Tours, Tours, France ; Departement of Dermatology, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France
Houben, Roland; Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany
Schrama, David; Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany
Interdisziplinäres Zentrum für Klinische Forschung Würzburg (IZKF B‐343), German Research Foundation (SCHR 1178/3‐1) and Ligue Nationale Contre le Cancer, Comités 16, 18, 28, HUGO Grant.
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