A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers
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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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These rearrangement patterns have been reported in breast cancer but not associated with germline predisposition.
“Whilst these patterns of rearrangements have been reported in BC [28, 29], they have not been associated with a germline predisposition.”
From Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers (2019) · cites this paper as [29]
More than 60% of breast cancers in germline TP53 carriers are ERBB2/HER2 amplified, and complex structural rearrangements are suggested to drive amplification in such cancers.
“Interestingly, >60% of BC in germline TP53 carriers are ERBB2/HER2 amplified [30] and complex structural rearrangements are suggested to drive amplification in such cancers [29].”
From Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers (2019) · cites this paper as [29]
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Validity of whole genomes sequencing results in neoplasms in precision medicine
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Melo, M. L., Fonseca, R., Pauli, F. P., Zavan, B., Hanemann, J. A. C., Miyazawa, M., Caixeta, E. S., Nacif, J. L. M., Aissa, A. F., Barreiro, E. J., et al. (2023) · Toxicology in Vitro · doi:10.1016/j.tiv.2023.105686 · Cited by 6 · see citing works
Pivot, X. B., Romieu, G., Fumoleau, P., Rios, M., Bonnefoi, H. R., Bachelot, T., Soulié, P., Jouannaud, C., Bourgeois, H. P., Petit, T., et al. (2017) · npj Breast Cancer · doi:10.1038/s41523-017-0005-y · Cited by 5 · see citing works
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- Authors
- Ferrari, A., Vincent-Salomon, A., Pivot, X., Sertier, A.-S., Thomas, E., Tonon, L., Boyault, S., Mulugeta, E., Treilleux, I., MacGrogan, G., Arnould, L., Kielbassa, J., Le Texier, V., Blanché, H., Deleuze, J.-F., Jacquemier, J., Mathieu, M.-C., Penault-Llorca, F., Bibeau, F., Mariani, O., Mannina, C., Pierga, J.-Y., Trédan, O., Bachelot, T., Bonnefoi, H., Romieu, G., Fumoleau, P., Delaloge, S., Rios, M., Ferrero, J.-M., Tarpin, C., Bouteille, C., Calvo, F., Gut, I. G., Gut, M., Martin, S., Nik-Zainal, S., Stratton, M. R., Pauporté, I., Saintigny, P., Birnbaum, D., Viari, A., & Thomas, G.
- Affiliations
- Centre Léon Bérard (FR)
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- Fondation Jean Dausset-CEPH (FR)
- Institut Paoli-Calmettes (FR)
- Institut Gustave Roussy (FR)
- Institut Regional du Cancer de Montpellier (FR)
- Université Paris Sciences et Lettres (FR)
- Institut Bergonié (FR)
- Centre Antoine Lacassagne (FR)
- Clinique Mutualiste Chirurgicale (FR)
- Universitat Pompeu Fabra (ES)
- Wellcome Sanger Institute (GB)
- Institut National du Cancer (FR)
- Institut national de recherche en sciences et technologies du numérique (FR)
- Corresponding author
- Ferrari, Anthony
- Viari, Alain
- ORCID
- Ferrari, Anthony
- Pivot, Xavier
- Sertier, Anne-Sophie
- Thomas, Emilie
- Tonon, Laurie
- Boyault, Sandrine
- Mulugeta, Eskeatnaf
- Treilleux, Isabelle
- MacGrogan, Gaëtan
- Arnould, Laurent
- Kielbassa, Janice
- Blanché, Hélène
- Deleuze, Jean-François
- Bibeau, Frédéric
- Mariani, Odette
- Pierga, Jean-Yves
- Trédan, Olivier
- Bachelot, Thomas
- Fumoleau, Pierre
- Delaloge, Suzette
- Ferrero, Jean-Marc
- Tarpin, Carole
- Bouteille, Catherine
- Calvo, Fabien
- Gut, Ivo Glynne
- Martin, Sancha
- Stratton, Michael R.
- Saintigny, Pierre
- Birnbaum, Daniel
- Viari, Alain
- Thomas, Gilles
- Venue
- Nature Communications
- Published
- 2016-07-13
- Volume
- 7
- Issue
- 1
- Pages
- 12222-12222
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4947184
- OpenAlex
- W2461625475
- Cited by
- 150
- References
- 71
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 14 · 2023: 16 · 2022: 10 · 2021: 14 · 2020: 28 · 2019: 19 · 2018: 13 · 2017: 11 · 2016: 6
- FWCI
- 8.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Apollo (cc-by)
- Funders
- Agence Nationale de la Recherche (ANR-11-BINF-0001)
- Institut National Du Cancer (INCa-4662)
- Topics
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- HER2-positive breast cancer, whole genome sequencing, transcriptome, tumor heterogeneity, somatic mutations, copy number alterations, structural variants, targeted therapy resistance, gene amplification
- MeSH terms
- Whole Genome Sequencing, Breast Neoplasms, Female, Gene Amplification, Humans, Mutation, Receptors, Progesterone, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, Polymorphism, Single Nucleotide, Gene Expression Profiling, Estrogen Receptor alpha, DNA Copy Number Variations, Transcriptome
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