title: Comparative epigenetic analyses reveal distinct patterns of oncogenic pathways activation in breast cancer subtypes.
abstract: Breast cancer is a highly heterogeneous disease that is characterized by genetic and epigenetic aberrations; however, our knowledge of epigenetic alterations of breast cancer subtypes remains limited. Here, we portrayed and compared the alterations of six types of histone modifications and DNA methylation between two breast cancer subtypes, luminal and basal. Widespread subtype-specific epigenetic alterations were observed in both subtypes, which preferentially occurred within CpG islands (CGIs) and promoter regions. Specifically, aberrant DNA methylation was mostly located inside CGIs in luminal subtype, whereas in basal subtype it was principally located within CGI shores. Moreover, different types and combinatorial patterns of epigenetic alterations were found to occupy at promoter regions between these two subtypes. And these epigenetic alterations regulated corresponding gene expression in a synergetic way in both subtypes. Functional enrichment analysis highlighted that epigenetically dysregulated genes were significantly involved in the hallmarks of cancers, most of which were subtype specific. Even genes involved in the same hallmarks associated biological processes were affected by various types of epi-modifications in different subtypes. Finally, we revealed distinct patterns of oncogenic pathways activation in different subtypes and provided novel insights into subtype specific therapeutic opportunities. In addition, genes in the key signaling pathways were able to discriminate between disease phenotypes, and subtype-specific progression associated genes were identified. This study presents the aberrant epigenetic patterns of breast cancer subtypes at a genome-wide level, which will be a highly valuable resource for investigations at understanding epigenetic regulation of breast cancer subtypes.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Shengli
authors.initials: S
authors.lastname: Li
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Shao
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Chunjie
authors.initials: C
authors.lastname: Jiang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China lixia@hrbmu.edu.cn xujuanbiocc@ems.hrbmu.edu.cn.
authors.forename: Juan
authors.initials: J
authors.lastname: Xu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China lixia@hrbmu.edu.cn xujuanbiocc@ems.hrbmu.edu.cn.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D011401:Promoter Regions, Genetic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D015398:Signal Transduction
chemical_list: D006657:Histones; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human