Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes

BMC Genomics

Jiejun Shi¹  Yuanxin Xi¹  Wei Li¹  W. Lee Kraus²  Hector L. Franco²  Venkat S. Malladi²  Anusha Nagari²  Melissa S. Simper³  Mark T. Bedford³  Luis Della Coletta³  Sharon Y. R. Dent³  Kaori Tanaka³  Jianjun Shen³  Jing Li³  Michelle C. Barton³  Kendra L. Allton³  Wenqian Li³  Xiaobing Shi³  Dana Richardson⁴  Khandan Keyomarsi⁴ 

[1] Department of Molecular and Cellular Biology and Division of Biostatistics, Dan L. Duncan Cancer Center, Baylor College of Medicine;Laboratory of Signaling and Gene Regulation, Cecil H. and Ida Green Center for Reproductive Biology Sciences and Division of Basic Reproductive Biology Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center;The Department of Epigenetics and Molecular Carcinogenesis, University of Texas Graduate School of Biomedical Sciences at Houston and The Center for Cancer Epigenetics, University of Texas M.D. Anderson Cancer Center;The Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center;

关键词: Breast cancer subtypes;    Epigenetics;    Histone modifications;    Chromatin states;   

DOI  :  10.1186/s12864-018-4533-0

来源: DOAJ

【 摘 要 】

Abstract Background Epigenetic regulators are frequently mutated or aberrantly expressed in a variety of cancers, leading to altered transcription states that result in changes in cell identity, behavior, and response to therapy. Results To define alterations in epigenetic landscapes in breast cancers, we profiled the distributions of 8 key histone modifications by ChIP-Seq, as well as primary (GRO-seq) and steady state (RNA-Seq) transcriptomes, across 13 distinct cell lines that represent 5 molecular subtypes of breast cancer and immortalized human mammary epithelial cells. Discussion Using combinatorial patterns of distinct histone modification signals, we defined subtype-specific chromatin signatures to nominate potential biomarkers. This approach identified AFAP1-AS1 as a triple negative breast cancer-specific gene associated with cell proliferation and epithelial-mesenchymal-transition. In addition, our chromatin mapping data in basal TNBC cell lines are consistent with gene expression patterns in TCGA that indicate decreased activity of the androgen receptor pathway but increased activity of the vitamin D biosynthesis pathway. Conclusions Together, these datasets provide a comprehensive resource for histone modification profiles that define epigenetic landscapes and reveal key chromatin signatures in breast cancer cell line subtypes with potential to identify novel and actionable targets for treatment.

【 授权许可】

Unknown