A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers.
A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers.
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DOI：
10.1038/ncomms12222
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发表时间：
2016-07-13
影响因子：
16.6
通讯作者：
Thomas G
中科院分区：
文献类型：
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作者：
Ferrari A;Vincent-Salomon A;Pivot X;Sertier AS;Thomas E;Tonon L;Boyault S;Mulugeta E;Treilleux I;MacGrogan G;Arnould L;Kielbassa J;Le Texier V;Blanché H;Deleuze JF;Jacquemier J;Mathieu MC;Penault-Llorca F;Bibeau F;Mariani O;Mannina C;Pierga JY;Trédan O;Bachelot T;Bonnefoi H;Romieu G;Fumoleau P;Delaloge S;Rios M;Ferrero JM;Tarpin C;Bouteille C;Calvo F;Gut IG;Gut M;Martin S;Nik-Zainal S;Stratton MR;Pauporté I;Saintigny P;Birnbaum D;Viari A;Thomas G
HER2阳性乳腺癌长期以来被证明是一种临床上截然不同的乳腺癌，现在有几种靶向治疗方法。然而，与特定基因表达或突变相关的治疗耐药性已经被观察到，这揭示了这些癌症的潜在多样性。因此，全面了解HER2阳性疾病的异质性仍然具有挑战性。在这里，我们对HER2阳性的乳腺肿瘤基因组进行了深入的基因组表征，基于表达数据，这些基因组表现出四个亚组，在体细胞突变、拷贝数变化或结构变异方面具有明显的基因组特征。结果表明，尽管临床上HER2阳性肿瘤是由特定的基因扩增来定义的，但HER2阳性肿瘤融合在整个管腔-基底乳腺癌谱中，而不是孤立地存在。结果还得到了106kb的ERBB2扩增子，并表明几种情况下的扩增符合断裂-融合-桥机制。根据HER2和激素受体的表达，乳腺癌被分为多个亚型。在此，作者报道了HER2阳性肿瘤的全基因组序列，并进一步将其分为四组，它们具有不同的基因表达谱和基因组特征。
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 cancer is separated into multiple subtypes based on the expression of HER2 and hormone receptors. Here, the authors report the whole genome sequence of 64 HER2 positive tumours and show that these can be further separated into four groups with different gene expression profiles and genomic features.