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Distinct Regulation of EZH2 and its Repressive H3K27me3 Mark in Polyomavirus-Positive and -Negative Merkel Cell Carcinoma.
Durand, Marie-Alice; Drouin, Aurélie; Mouchard, Alice; Durand, Laurine; Esnault, Clara; Berthon, Patricia; Tallet, Anne; Le Corre, Yannick; Hainaut-Wierzbicka, Ewa; Blom, Astrid; Saiag, Philippe; Beneton, Nathalie; Bens, Guido; Nardin, Charlee; Aubin, François; Dinulescu, Monica; Collin, Christine; Fromont-Hankard, Gaëlle; Cribier, Bernard; Laurent-Roussel, Sara; Cokelaere, Kristof; Houben, Roland; Schrama, David; Peixoto, Paul; Hervouet, Eric; Bachiri, Kamel; Kantar, Diala; Coyaud, Etienne; Guyétant, Serge; Samimi, Mahtab; Touzé, Antoine; Kervarrec, Thibault.
Afiliación
  • Durand MA; Team "Biologie des Infections à Polyomavirus", ISP UMR 1282, INRAE, University of Tours, Tours, France.
  • Drouin A; Team "Biologie des Infections à Polyomavirus", ISP UMR 1282, INRAE, University of Tours, Tours, France.
  • Mouchard A; Team "Biologie des Infections à Polyomavirus", ISP UMR 1282, INRAE, University of Tours, Tours, France; Department of Dermatology, CHRU of Tours, University of Tours, Chambray-lès-Tours, France.
  • Durand L; Team "Biologie des Infections à Polyomavirus", ISP UMR 1282, INRAE, University of Tours, Tours, France.
  • Esnault C; Team "Biologie des Infections à Polyomavirus", ISP UMR 1282, INRAE, University of Tours, Tours, France.
  • Berthon P; Team "Biologie des Infections à Polyomavirus", ISP UMR 1282, INRAE, University of Tours, Tours, France.
  • Tallet A; Platform of Somatic Tumor Molecular Genetics, CHU of Tours, University of Tours, Tours, France.
  • Le Corre Y; Dermatology Department, CHU of Angers, LUNAM University, Angers, France.
  • Hainaut-Wierzbicka E; Dermatology Department, CHU of Poitiers, University of Poitiers, Poitiers, France.
  • Blom A; Department of General and Oncologic Dermatology, Ambroise-Paré Hospital, CARADERM Network, Boulogne-Billancourt, France; Research unit EA 4340, University of Versailles-Saint-Quentin-en-Yvelines, Paris-Saclay University, Boulogne-Billancourt, France.
  • Saiag P; Department of General and Oncologic Dermatology, Ambroise-Paré Hospital, CARADERM Network, Boulogne-Billancourt, France; Research unit EA 4340, University of Versailles-Saint-Quentin-en-Yvelines, Paris-Saclay University, Boulogne-Billancourt, France.
  • Beneton N; Dermatology Department, CHU of Le Mans, University of Le Mans, Le Mans, France.
  • Bens G; Dermatology department, CHR Orleans, Orleans, France.
  • Nardin C; Dermatology, CHU Besançon, Besançon, France; INSERM 1098, Université Bourgogne Franche-Comté, Besançon, France.
  • Aubin F; Dermatology, CHU Besançon, Besançon, France; INSERM 1098, Université Bourgogne Franche-Comté, Besançon, France.
  • Dinulescu M; Dermatology department, CHU Rennes, Institut Dermatologique du Grand Ouest (IDGO), Rennes, France.
  • Collin C; Platform of Somatic Tumor Molecular Genetics, CHU of Tours, University of Tours, Tours, France.
  • Fromont-Hankard G; Pathology Department, CHU of Tours, University of Tours, Tours, France.
  • Cribier B; Dermatology Department, CHU of Strasbourg, University of Strasbourg, Strasbourg, France.
  • Laurent-Roussel S; Paris - La roquette, National Dermatopathology Center, Paris, France.
  • Cokelaere K; Pathology Department, Regional Hospital Jan Yperman, Ieper, Belgium.
  • Houben R; Department of Dermatology, Venerology and Allergology, University Hospital of Würzburg, Würzburg, Germany.
  • Schrama D; Department of Dermatology, Venerology and Allergology, University Hospital of Würzburg, Würzburg, Germany.
  • Peixoto P; INSERM, EFS-BFC, UMR 1098 RIGHT, University Bourgogne-Franche-Comté, Besançon, France; EPIgenetics and GENe Expression Technical Platform (EPIGENExp), University Bourgogne Franche-Comté, Besançon, France.
  • Hervouet E; INSERM, EFS-BFC, UMR 1098 RIGHT, University Bourgogne-Franche-Comté, Besançon, France; EPIgenetics and GENe Expression Technical Platform (EPIGENExp), University Bourgogne Franche-Comté, Besançon, France.
  • Bachiri K; Department of Biology, Inserm U1192, Protéomique Réponse Inflammatoire Spectrométrie de Masse-PRISM, CHU Lille, Université de Lille, Lille, France.
  • Kantar D; Department of Biology, Inserm U1192, Protéomique Réponse Inflammatoire Spectrométrie de Masse-PRISM, CHU Lille, Université de Lille, Lille, France.
  • Coyaud E; Department of Biology, Inserm U1192, Protéomique Réponse Inflammatoire Spectrométrie de Masse-PRISM, CHU Lille, Université de Lille, Lille, France.
  • Guyétant S; Pathology Department, CHU of Tours, University of Tours, Tours, France; Team "Biologie des Infections à Polyomavirus", ISP UMR 1282, INRAE, University of Tours, Tours, France.
  • Samimi M; Team "Biologie des Infections à Polyomavirus", ISP UMR 1282, INRAE, University of Tours, Tours, France; Department of Dermatology, CHRU of Tours, University of Tours, Chambray-lès-Tours, France.
  • Touzé A; Team "Biologie des Infections à Polyomavirus", ISP UMR 1282, INRAE, University of Tours, Tours, France.
  • Kervarrec T; Team "Biologie des Infections à Polyomavirus", ISP UMR 1282, INRAE, University of Tours, Tours, France; Pathology Department, CHU of Tours, University of Tours, Tours, France. Electronic address: thibaultkervarrec@yahoo.fr.
J Invest Dermatol ; 143(10): 1937-1946.e7, 2023 10.
Article en En | MEDLINE | ID: mdl-37037414
Merkel cell carcinoma (MCC) is an aggressive skin cancer for which Merkel cell polyomavirus integration and expression of viral oncogenes small T and Large T have been identified as major oncogenic determinants. Recently, a component of the PRC2 complex, the histone methyltransferase enhancer of zeste homolog 2 (EZH2) that induces H3K27 trimethylation as a repressive mark has been proposed as a potential therapeutic target in MCC. Because divergent results have been reported for the levels of EZH2 and trimethylation of lysine 27 on histone 3, we analyzed these factors in a large MCC cohort to identify the molecular determinants of EZH2 activity in MCC and to establish MCC cell lines' sensitivity to EZH2 inhibitors. Immunohistochemical expression of EZH2 was observed in 92% of MCC tumors (156 of 170), with higher expression levels in virus-positive than virus-negative tumors (P = 0.026). For the latter, we showed overexpression of EZHIP, a negative regulator of the PRC2 complex. In vitro, ectopic expression of the large T antigen in fibroblasts led to the induction of EZH2 expression, whereas the knockdown of T antigens in MCC cell lines resulted in decreased EZH2 expression. EZH2 inhibition led to selective cytotoxicity on virus-positive MCC cell lines. This study highlights the distinct mechanisms of EZH2 induction between virus-negative and -positive MCC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Cutáneas / Carcinoma de Células de Merkel / Poliomavirus de Células de Merkel Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Invest Dermatol Año: 2023 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Cutáneas / Carcinoma de Células de Merkel / Poliomavirus de Células de Merkel Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Invest Dermatol Año: 2023 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos