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Journal Articles Nature Communications Year : 2016

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

1 Centre Léon Bérard [Lyon]
2 Génétique et Biologie du Développement
3 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
4 VINCO - Validation et identification de nouvelles cibles en oncologie
5 LNC - Lipides - Nutrition - Cancer (U866)
6 Département de Biologie et pathologie des tumeurs [Centre Georges-François Leclerc]
7 CEPH - Centre d'Etude du Polymorphisme Humain
8 IPC - Institut Paoli-Calmettes
9 IGR - Institut Gustave Roussy
10 ERTICa - Equipe de recherche sur les traitements individualisés des cancers
11 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
12 Centre de Ressources Biologiques [Paris]
13 Département de pathologie
14 PCC - Physico-Chimie-Curie
15 UPD5 - Université Paris Descartes - Paris 5
16 Department of Medical Oncology [Lyon]
17 ICM - UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle
18 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
19 Pathologie mammaire
20 UNICANCER/ICL - Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy]
21 Pôle de Chirurgie Oncologique générale, Gynécologique et Mammaire [Centre Antoine-Lacassagne]
22 CRCM - Centre de Recherche en Cancérologie de Marseille
23 Chirurgie gynécologique, mammaire et réparatrice [Saint-Etienne]
24 Direction de la recherche [Gustave Roussy]
25 CRG - Centre for Genomic Regulation - Centre de Regulació Genòmica [Barcelona]
26 The Wellcome Trust Sanger Institute [Cambridge]
27 INCa - Institut national du cancer
28 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
29 ERABLE - Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale
Sandrine Boyault
  • Function : Author
  • PersonId : 757688
  • IdRef : 075706466
Jean-François Deleuze
  • Function : Author
  • PersonId : 1015006
Olivier Trédan
Thomas Bachelot
Suzette Delaloge

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.
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Dates and versions

hal-01388446 , version 1 (12-07-2017)

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Anthony Ferrari, Anne Vincent-Salomon, Xavier Pivot, Anne-Sophie Sertier, Emile Thomas, et al.. A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers. Nature Communications, 2016, 7, pp.Article number: 12222. ⟨10.1038/ncomms12222⟩. ⟨hal-01388446⟩
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