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

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...

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Detalles Bibliográficos
Autores principales: Xi, Yuanxin, Shi, Jiejun, Li, Wenqian, Tanaka, Kaori, Allton, Kendra L., Richardson, Dana, Li, Jing, Franco, Hector L., Nagari, Anusha, Malladi, Venkat S., Coletta, Luis Della, Simper, Melissa S., Keyomarsi, Khandan, Shen, Jianjun, Bedford, Mark T., Shi, Xiaobing, Barton, Michelle C., Kraus, W. Lee, Li, Wei, Dent, Sharon Y. R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819162/
https://www.ncbi.nlm.nih.gov/pubmed/29458327
http://dx.doi.org/10.1186/s12864-018-4533-0
Descripción
Sumario: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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-4533-0) contains supplementary material, which is available to authorized users.