Chen Xiaohua, Hu Hanyang, He Lin, Yu Xueyuan, Liu Xiangyu, Zhong Rong, Shu Maoguo
Departmemt of Plastic, Aesthetic and Craniofacial Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Department of Laboratory Medicine, No.161 Hospital of PLA, Wuhan, 430010, China.
Breast Cancer Res Treat. 2016 Jun;157(2):267-279. doi: 10.1007/s10549-016-3826-8. Epub 2016 May 13.
Breast cancer has been classified into several intrinsic molecular subtypes on the basis of genetic and epigenetic factors. However, knowledge about histone modifications that contribute to the classification and development of biologically distinct breast cancer subtypes remains limited. Here we compared the genome-wide binding patterns of H3K4me3 and H3K27me3 between human mammary epithelial cells and three breast cancer cell lines representing the luminal, HER2, and basal subtypes. We characterized thousands of unique binding events as well as bivalent chromatin signatures unique to each cancer subtype, which were involved in different epigenetic regulation programs and signaling pathways in breast cancer progression. Genes linked to the unique histone mark features exhibited subtype-specific expression patterns, both in cancer cell lines and primary tumors, some of which were confirmed by qPCR in our primary cancer samples. Finally, histone mark-based gene classifiers were significantly correlated with relapse-free survival outcomes in patients. In summary, we have provided a valuable resource for the identification of novel biomarkers of subtype classification and clinical prognosis evaluation in breast cancers.
基于遗传和表观遗传因素，乳腺癌已被分为几种内在分子亚型。然而，关于有助于生物学上不同的乳腺癌亚型分类和发展的组蛋白修饰的知识仍然有限。在这里，我们比较了人乳腺上皮细胞与代表管腔型、HER2型和基底型亚型的三种乳腺癌细胞系之间H3K4me3和H3K27me3的全基因组结合模式。我们鉴定了数千个独特的结合事件以及每种癌症亚型特有的二价染色质特征，这些特征参与了乳腺癌进展中不同的表观遗传调控程序和信号通路。与独特组蛋白标记特征相关的基因在癌细胞系和原发性肿瘤中均表现出亚型特异性表达模式，其中一些在我们的原发性癌症样本中通过qPCR得到了证实。最后，基于组蛋白标记的基因分类器与患者的无复发生存结果显著相关。总之，我们为鉴定乳腺癌亚型分类和临床预后评估的新型生物标志物提供了宝贵资源。
