title: A novel subtype classification and risk of breast cancer by histone modification profiling.
abstract: 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.
authors.affiliation: 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.|School of Basic Medical Science, Wuhan University, Wuhan, 430071, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Basic Medical Science, Wuhan University, Wuhan, 430071, China.
authors.forename: Hanyang
authors.initials: H
authors.lastname: Hu
authors.affiliation: Departmemt of Plastic, Aesthetic and Craniofacial Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.affiliation: Departmemt of Plastic, Aesthetic and Craniofacial Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Yu
authors.affiliation: Departmemt of Plastic, Aesthetic and Craniofacial Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Epidemiology and Biostatistics and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.affiliation: Departmemt of Plastic, Aesthetic and Craniofacial Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China. shumaoguo@163.com.|Department of Plastic Surgery, Xijing Hospital, Forth Military Medical University, Xi'an, 710032, China. shumaoguo@163.com.
authors.forename: Maoguo
authors.initials: M
authors.lastname: Shu
mesh_terms: D001943:Breast Neoplasms / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D042421:Histone Code; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D017423:Sequence Analysis, RNA; D016019:Survival Analysis
chemical_list: D006657:Histones
keywords: Bivalent chromatin; Breast cancer; Histone modification; Subtype classification