Epigenetic portraits of human breast cancers (various cell lines methylation data). Homo sapiens

Breast cancer is a molecularly, biologically and clinically heterogeneous group of disorders. Understanding this diversity is essential to improving diagnosis and optimising treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but information is scant on the involvement of the epigenome in breast cancer and its contribution to the complexity of the disease. Here we used the Infinium Methylation Platform to profile at single-CpG resolution (over 14,000 genes interrogated) the methylomes of 119 breast tumours. It emerges that many genes whose expression is linked to the ER status are epigenetically controlled (or/ we show that the two major phenotypes of breast cancers determined by ER status are widely involving epigenetic regulatory mechanisms), offering the prospect of a novel approach to treating ER-positive tumours. We have distinguished methylation-profile-based tumour clusters, some coinciding with known “expression subtypes” but also new entities that may provide a meaningful basis for refining breast tumour typology. We show that methylation patterns may reflect the cellular origins of tumours. Having highlighted an unexpectedly strong epigenetic component in the regulation of key immune pathways, we show that a set of immune genes have high prognostic value in specific tumour categories. By laying the ground for better understanding of breast cancer heterogeneity and improved tumour taxonomy, the precise epigenetic portraits drawn here should contribute to better management of breast cancer patients. Overall design: Gene expression profiling cell lines. Study of epigenetic variation (methylation) linked to gene expression. No replicate, no reference sample.

乳腺癌是一类在分子层面、生物学层面及临床层面均呈现异质性的疾病群。解析该疾病的异质性，对于优化乳腺癌的诊断方案与治疗策略至关重要。遗传异常与获得性表观遗传异常均参与癌症发生，但目前关于表观基因组在乳腺癌中的作用及其对疾病复杂性的贡献的相关研究仍较为匮乏。本研究使用Infinium甲基化芯片平台（Infinium Methylation Platform），以单CpG分辨率（覆盖超过14000个检测基因）对119例乳腺肿瘤的甲基化组进行了谱图分析。研究发现，诸多与雌激素受体（Estrogen Receptor, ER）状态相关的基因表达受表观遗传调控（本研究证实，由ER状态决定的乳腺癌两大主要表型广泛涉及表观遗传调控机制），这为ER阳性乳腺癌的新型治疗方案提供了潜在可能。本研究基于甲基化谱区分出了肿瘤聚类簇，其中部分与已知的“表达亚型”相契合，同时还发现了新的肿瘤亚型，这些结果可为细化乳腺肿瘤分型提供有价值的依据。研究证实，甲基化模式可反映肿瘤的细胞起源。本研究还揭示了关键免疫通路调控中存在出人意料的强表观遗传调控组分，并证实一组免疫基因在特定肿瘤类别中具有较高的预后价值。本研究为更深入解析乳腺癌异质性、优化肿瘤分类体系奠定了基础，本研究中绘制的精准表观遗传图谱将有助于改善乳腺癌患者的临床管理。实验整体设计：对细胞系开展基因表达谱分析；研究与基因表达相关的表观遗传变异（甲基化）；未设置生物学重复，亦无参照样本。