Department of Oncogenetics, Centre Jean Perrin, CBRV, 28 place Henri-Dunant, 63001, Clermont-Ferrand, France.
INSERM U 1240, IMOST, 58 rue Montalembert-BP184, 63005, Clermont-Ferrand, France.
Sci Rep. 2017 Jul 26;7(1):6597. doi: 10.1038/s41598-017-06790-z.
Breast cancer is a heterogeneous disease due to its clinico-pathological features and response to therapy. The classification of breast tumors based on their hormone receptor status and pathologic features. Post-translational histone modifications come into prominence for regulation of gene expression in cancer pathogenesis. Here, we analyzed dysregulation of H3K9ac and H3K27me3-enriched subtype-specific genes using ChIP-on-chip assay in breast cancer tumors and matched normal tissue samples. Breast cancer tumors were classified according to St Gallen Consensus 2013. Our results indicated that the promoter regions of genes modified by H3K9ac epi-mark are commonly associated with tumors with HER2-positive and TNBC subtype. H3K27me3-enriched genes were comprised of Luminal A and B1 subtypes. We constructed a network structure to elicit epigenetically regulated genes related with breast cancer progression. The central genes of the network (RUNX1, PAX3, GATA4 and DLX5) were subjected for epigenetically dysregulation in association with different breast cancer subtypes. Our study submits epigenetic mechanisms are crucial to elicit subtype-specific regulation in breast cancer and ChIP-on-chip assay provides a better understanding for breast tumorigenesis and new approaches for prevention and treatment.
乳腺癌是一种异质性疾病，其临床病理特征和对治疗的反应各不相同。基于激素受体状态和病理特征对乳腺肿瘤进行分类。组蛋白翻译后修饰在癌症发病机制中的基因表达调控中变得尤为重要。在这里，我们使用 ChIP-on-chip 分析了乳腺癌肿瘤和配对的正常组织样本中 H3K9ac 和 H3K27me3 富集的亚类特异性基因的失调。乳腺癌根据 2013 年圣加仑共识进行分类。我们的结果表明，H3K9ac epi 标记修饰的基因启动子区域通常与 HER2 阳性和 TNBC 亚型的肿瘤相关。H3K27me3 富集的基因包括 Luminal A 和 B1 亚型。我们构建了一个网络结构，以阐明与乳腺癌进展相关的受表观遗传调控的基因。该网络的核心基因（RUNX1、PAX3、GATA4 和 DLX5）与不同的乳腺癌亚型相关的表观遗传失调。我们的研究表明，表观遗传机制对于引出乳腺癌的亚型特异性调控至关重要，而 ChIP-on-chip 分析为乳腺癌的发生提供了更好的理解，并为预防和治疗提供了新的方法。
