Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, USA.
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
Sci Rep. 2018 Apr 3;8(1):5535. doi: 10.1038/s41598-018-24005-x.
Malignant breast cancer remains a major health threat to women of all ages worldwide and epigenetic variations on DNA methylation have been widely reported in cancers of different types. We profiled DNA methylation with ERRBS (Enhanced Reduced Representation Bisulfite Sequencing) across four main stages of tumor progression in the MMTV-PyMT mouse model (hyperplasia, adenoma/mammary intraepithelial neoplasia, early carcinoma and late carcinoma), during which malignant transition occurs. We identified a large number of differentially methylated cytosines (DMCs) in tumors relative to age-matched normal mammary glands from FVB mice. Despite similarities, the methylation differences of the premalignant stages were distinct from the malignant ones. Many differentially methylated loci were preserved from the first to the last stage throughout tumor progression. Genes affected by methylation gains were enriched in Polycomb repressive complex 2 (PRC2) targets, which may present biomarkers for early diagnosis and targets for treatment.
乳腺癌仍然是全球各年龄段女性的主要健康威胁，不同类型癌症中的 DNA 甲基化的表观遗传变化已被广泛报道。我们通过 MMTV-PyMT 小鼠模型（增生、腺瘤/乳腺上皮内瘤变、早期癌和晚期癌）中肿瘤进展的四个主要阶段（增生、腺瘤/乳腺上皮内瘤变、早期癌和晚期癌）进行了全基因组 DNA 甲基化的 ERRBS（增强的简化重亚硫酸盐测序）分析，在此期间发生恶性转化。我们在 MMTV-PyMT 小鼠模型中鉴定到大量与 FVB 小鼠年龄匹配的正常乳腺组织相比在肿瘤中发生差异甲基化的胞嘧啶（DMC）。尽管存在相似性，但癌前阶段的甲基化差异与恶性阶段的甲基化差异明显不同。许多差异甲基化的基因座在肿瘤进展的整个过程中从第一阶段到最后阶段都得到了保留。受甲基化增益影响的基因在多梳抑制复合物 2（PRC2）靶基因中富集，这些基因可能成为早期诊断的标志物和治疗的靶点。
