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

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Ferrari, Anthony 
Vincent-Salomon, Anne 
Pivot, Xavier 
Sertier, Anne-Sophie 
Thomas, Emilie 

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.

Breast Neoplasms, DNA Copy Number Variations, Estrogen Receptor alpha, Female, Gene Amplification, Gene Expression Profiling, Humans, Mutation, Polymorphism, Single Nucleotide, Receptor, ErbB-2, Receptors, Progesterone, Transcriptome, Whole Genome Sequencing
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Nat Commun
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Springer Science and Business Media LLC