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Nat Commun. 2016 Jul 13;7:12222. doi: 10.1038/ncomms12222.

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

Author information

1
Synergie Lyon Cancer, Plateforme de bioinformatique 'Gilles Thomas' Centre Léon Bérard, 28 rue Laënnec, 69008 Lyon, France.
2
Institut Curie, PSL Research University, Département de Pathologie, INSERM U934, 26 rue d'Ulm, 75248 Paris, France.
3
Centre Hospitalier Universitaire de Minjoz, UMR INSERM 1098, Boulevard A. Fleming, Besançon 25000, France.
4
Plateforme de génomique des cancers, Centre Léon Bérard, 28 rue Laënnec, 69008 Lyon, France.
5
Institut Curie, UMR 3215 CNRS, Génétique et biologie du développement, Epigénèse et développement des mammifères, U934 Inserm, 26 rue d'Ulm, 75248 Paris, France.
6
Centre Léon Bérard, Département de Pathologie, 28 rue Laënnec, 69008 Lyon, France.
7
Département de Biopathologie, Unité Inserm U916, Institut Bergonié, 229 cours de l'Argonne, 33076 Bordeaux, France.
8
Centre Georges-François Leclerc et CRB Ferdinand Cabanne, 1 rue du Professeur Marion, Inserm U866-UBFC, 21000 Dijon, France.
9
Centre d'Etude du Polymorphisme Humain (CEPH), Fondation Jean Dausset, 27 rue Juliette Dodu, 75010 Paris, France.
10
Institut Paoli-Calmettes, Département de Pathologie, 232 Boulevard de Sainte-Marguerite, 13009 Marseille, France.
11
Institut Gustave Roussy, Comité de Pathologie Mammaire, 114 rue Edouard Vaillant, 94805 Villejuif, France.
12
Centre Jean Perrin, Département de Biopathologie, EA 4677 ERTICa, Université d'Auvergne, 58 rue Montalembert, 63000 Clermont-Ferrand, France.
13
Institut Régional du Cancer de Montpellier (ICM), Département de Pathologie, 208 Avenue des Apothicaires, 34298 Montpellier, France.
14
Institut Curie, PSL Research University, Service de Pathologie, Centre de Ressources Biologiques, BRIF BB-0033-00048, 26 rue d'Ulm, 75248 Paris, France.
15
Département de Pathologie, Institut Bergonié, 229 cours de l'Argonne, CS 61283, 33076 Bordeaux, France.
16
Institut Curie, PSL Research University, Département d'Oncologie Médicale, Université Paris Descartes, 26 rue d'Ulm, 75248 Paris, France.
17
Centre Léon Bérard, Département de Cancérologie Médicale, 28 rue Laënnec, 69008 Lyon, France.
18
Department of Medical Oncology, Institut Bergonié Unicancer, University of Bordeaux, INSERM U916, CIC1401, 229 cours de l'Argonne, CS 61283, 33076 Bordeaux, France.
19
Institut Régional du Cancer de Montpellier (ICM), Oncologie Sénologie, 208 Avenue des Apothicaires, 34298 Montpellier, France.
20
Centre Alexis Vautrin, Département d'Oncologie Médicale, 6 Avenue de Bourgogne, 54511 Vandoeuvre Les Nancy, France.
21
Centre Antoine Lacassagne, Département d'Oncologie Médicale, 33 Avenue de Valombrose, 06189 Nice, France.
22
Institut Paoli-Calmettes, Département d'Oncologie Médicale, 232 Boulevard de Sainte-Marguerite, 13009 Marseille, France.
23
Clinique Mutualiste de Bellevue, Chirurgie Gynécologique et Mammaire, 3 rue le Verrier, 42100 Saint-Etienne, France.
24
Institut Gustave Roussy, Cancer Core Europe, 39 rue Camille Desmoulins, Villejuif 94805, France.
25
CNAG-CRG, Centre for Genomic Regulation (CRG), C/Baldiri Reixac 4, 08028 Barcelona, Spain.
26
Universitat Pompeu Fabra, Plaça de la Mercè, 10, 08002 Barcelona, Spain.
27
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
28
East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 9NB, UK.
29
Institut National du Cancer, Département de Recherche Clinique, 52 Avenue Morizet, 92513 Boulogne-Billancourt, France.
30
INSERM U1052-CNRS 5286, Cancer Research Center of Lyon, F-69008 Lyon, France.
31
Université de Lyon, F-69622 Lyon, France.
32
Centre Léon Bérard, 28 rue Laënnec, 69008 Lyon, France.
33
Département d'Oncologie Moléculaire, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille, INSERM, CNRS, Aix-Marseille Université, 232 boulevard de Sainte-Marguerite, 13009 Marseille, France.
34
Equipe Erable, INRIA Grenoble-Rhône-Alpes, 655 Avenue de l'Europe, 38330 Montbonnot-Saint Martin, France.

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.

PMID:
27406316
PMCID:
PMC4947184
DOI:
10.1038/ncomms12222
[Indexed for MEDLINE]
Free PMC Article

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