Epigenetics Laboratory, Research Centre for Medical Genetics, Moscow, Russia.
Molecular & Cell Genetics Department, Pirogov Russian National Research Medical University, Moscow, Russia.
Epigenomics. 2019 May;11(6):605-617. doi: 10.2217/epi-2018-0213. Epub 2019 Feb 7.
To provide a breast cancer (BC) methylotype classification by genome-wide CpG islands bisulfite DNA sequencing. XmaI-reduced representation bisulfite sequencing DNA methylation sequencing method was used to profile DNA methylation of 110 BC samples and 6 normal breast samples. Intrinsic DNA methylation BC subtypes were elicited by unsupervised hierarchical cluster analysis, and cluster-specific differentially methylated genes were identified. Overall, six distinct BC methylotypes were identified. BC cell lines constitute a separate group extremely highly methylated at the CpG islands. In turn, primary BC samples segregate into two major subtypes, highly and moderately methylated. Highly and moderately methylated superclusters, each incorporate three distinct epigenomic BC clusters with specific features, suggesting novel perspectives for personalized therapy.
通过全基因组 CpG 岛亚硫酸氢盐测序提供乳腺癌 (BC) 的甲基化分型。使用 XmaI 减少代表性亚硫酸氢盐测序 DNA 甲基化测序方法对 110 个 BC 样本和 6 个正常乳腺样本的 DNA 甲基化进行了分析。通过无监督层次聚类分析得出内在 DNA 甲基化 BC 亚型，并确定了聚类特异性差异甲基化基因。总体而言，鉴定出了六个不同的 BC 甲基化类型。BC 细胞系在 CpG 岛高度甲基化，形成一个独立的组。反过来，原发性 BC 样本分为高度和中度甲基化两个主要亚型。高度和中度甲基化超群簇，每个簇包含三个具有特定特征的不同表观基因组 BC 簇，为个性化治疗提供了新的视角。
