A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers

Anthony Ferrari (), Anne Vincent-Salomon, Xavier Pivot, Anne-Sophie Sertier, Emilie Thomas, Laurie Tonon, Sandrine Boyault, Eskeatnaf Mulugeta, Isabelle Treilleux, Gaëtan MacGrogan, Laurent Arnould, Janice Kielbassa, Vincent Le Texier, Hélène Blanché, Jean-François Deleuze, Jocelyne Jacquemier, Marie-Christine Mathieu, Frédérique Penault-Llorca, Frédéric Bibeau, Odette Mariani, Cécile Mannina, Jean-Yves Pierga, Olivier Trédan, Thomas Bachelot, Hervé Bonnefoi, Gilles Romieu, Pierre Fumoleau, Suzette Delaloge, Maria Rios, Jean-Marc Ferrero, Carole Tarpin, Catherine Bouteille, Fabien Calvo, Ivo Glynne Gut, Marta Gut, Sancha Martin, Serena Nik-Zainal, Michael R. Stratton, Iris Pauporté, Pierre Saintigny, Daniel Birnbaum, Alain Viari () and Gilles Thomas
Additional contact information
Anthony Ferrari: Synergie Lyon Cancer, Plateforme de bioinformatique ‘Gilles Thomas’ Centre Léon Bérard
Anne Vincent-Salomon: Institut Curie, PSL Research University
Xavier Pivot: Centre Hospitalier Universitaire de Minjoz
Anne-Sophie Sertier: Synergie Lyon Cancer, Plateforme de bioinformatique ‘Gilles Thomas’ Centre Léon Bérard
Emilie Thomas: Synergie Lyon Cancer, Plateforme de bioinformatique ‘Gilles Thomas’ Centre Léon Bérard
Laurie Tonon: Synergie Lyon Cancer, Plateforme de bioinformatique ‘Gilles Thomas’ Centre Léon Bérard
Sandrine Boyault: Plateforme de génomique des cancers, Centre Léon Bérard
Eskeatnaf Mulugeta: Institut Curie, UMR 3215 CNRS, Génétique et biologie du développement, Epigénèse et développement des mammifères
Isabelle Treilleux: Centre Léon Bérard
Gaëtan MacGrogan: Unité Inserm U916, Institut Bergonié
Laurent Arnould: Centre Georges-François Leclerc et CRB Ferdinand Cabanne
Janice Kielbassa: Synergie Lyon Cancer, Plateforme de bioinformatique ‘Gilles Thomas’ Centre Léon Bérard
Vincent Le Texier: Synergie Lyon Cancer, Plateforme de bioinformatique ‘Gilles Thomas’ Centre Léon Bérard
Hélène Blanché: Centre d'Etude du Polymorphisme Humain (CEPH), Fondation Jean Dausset
Jean-François Deleuze: Centre d'Etude du Polymorphisme Humain (CEPH), Fondation Jean Dausset
Jocelyne Jacquemier: Institut Paoli-Calmettes
Marie-Christine Mathieu: Institut Gustave Roussy, Comité de Pathologie Mammaire
Frédérique Penault-Llorca: Centre Jean Perrin, EA 4677 ERTICa, Université d'Auvergne
Frédéric Bibeau: Institut Régional du Cancer de Montpellier (ICM)
Odette Mariani: Institut Curie, PSL Research University, Service de Pathologie, Centre de Ressources Biologiques
Cécile Mannina: Institut Bergonié
Jean-Yves Pierga: Institut Curie, PSL Research University, Université Paris Descartes
Olivier Trédan: Centre Léon Bérard
Thomas Bachelot: Centre Léon Bérard
Hervé Bonnefoi: Institut Bergonié Unicancer, University of Bordeaux
Gilles Romieu: Institut Régional du Cancer de Montpellier (ICM), Oncologie Sénologie
Pierre Fumoleau: Centre Georges-François Leclerc et CRB Ferdinand Cabanne
Suzette Delaloge: Institut Gustave Roussy, Comité de Pathologie Mammaire
Maria Rios: Centre Alexis Vautrin
Jean-Marc Ferrero: Centre Antoine Lacassagne
Carole Tarpin: Institut Paoli-Calmettes
Catherine Bouteille: Clinique Mutualiste de Bellevue, Chirurgie Gynécologique et Mammaire
Fabien Calvo: Institut Gustave Roussy, Cancer Core Europe
Ivo Glynne Gut: CNAG-CRG, Centre for Genomic Regulation (CRG)
Marta Gut: CNAG-CRG, Centre for Genomic Regulation (CRG)
Sancha Martin: Wellcome Trust Sanger Institute
Serena Nik-Zainal: Wellcome Trust Sanger Institute
Michael R. Stratton: Wellcome Trust Sanger Institute
Iris Pauporté: Institut National du Cancer
Pierre Saintigny: INSERM U1052-CNRS 5286, Cancer Research Center of Lyon
Daniel Birnbaum: Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille
Alain Viari: Synergie Lyon Cancer, Plateforme de bioinformatique ‘Gilles Thomas’ Centre Léon Bérard
Gilles Thomas: Synergie Lyon Cancer, Plateforme de bioinformatique ‘Gilles Thomas’ Centre Léon Bérard

Nature Communications, 2016, vol. 7, issue 1, 1-9

Abstract: Abstract HER2-positive breast cancer has long proven to be a clinically distinct class of breast cancers for which several targeted therapies are now available. However, resistance to the treatment associated with specific gene expressions or mutations has been observed, revealing the underlying diversity of these cancers. Therefore, understanding the full extent of the HER2-positive disease heterogeneity still remains challenging. Here we carry out an in-depth genomic characterization of 64 HER2-positive breast tumour genomes that exhibit four subgroups, based on the expression data, with distinctive genomic features in terms of somatic mutations, copy-number changes or structural variations. The results suggest that, despite being clinically defined by a specific gene amplification, HER2-positive tumours melt into the whole luminal–basal breast cancer spectrum rather than standing apart. The results also lead to a refined ERBB2 amplicon of 106 kb and show that several cases of amplifications are compatible with a breakage–fusion–bridge mechanism.

Date: 2016
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DOI: 10.1038/ncomms12222

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