Epigenetic portraits of human breast cancers (various cell lines expression data)

"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. 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、生物学及临床层面均呈现异质性的疾病集合。明晰此类异质性，对于优化乳腺癌的诊断与治疗方案至关重要。遗传异常与获得性表观遗传异常均参与癌症发生发展，但目前关于表观基因组（epigenome）在乳腺癌中的作用及其对疾病复杂性的贡献，相关研究仍较为匮乏。本研究采用Infinium甲基化检测平台（Infinium Methylation Platform），以单CpG分辨率对119例乳腺肿瘤的甲基化组进行了图谱分析，共检测超过14000个基因。研究发现，诸多与雌激素受体（Estrogen Receptor, ER）状态相关的基因受表观遗传调控；本研究同时证实，由ER状态划分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策略提供了可行方向。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（expression subtypes）相契合，同时也发现了新的肿瘤亚型，这些结果可为完善乳腺肿瘤分型体系提供重要依据。研究表明，甲基化模式可反映肿瘤的细胞起源。本研究揭示了关键免疫通路调控中存在出乎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。本研究为深入解析乳腺癌异质性、完善肿瘤分类体系奠定了基础，本研究获得的精准表观遗传图谱将有助于优化乳腺癌患者的临床管理。本研究开展了细胞系基因表达谱分析，以及与基因表达相关的表观遗传变异（甲基化）研究，且未设置生物学重复与参照样本。