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Genes Chromosomes Cancer. 2019 Mar 15. doi: 10.1002/gcc.22731. [Epub ahead of print]

Higher order genomic organization and epigenetic control maintain cellular identity and prevent breast cancer.

Fritz AJ1,2,3, Gillis NE1,3,4, Gerrard DL5,6, Rodriguez PD5,6, Hong D7, Rose JT1,2,3, Ghule PN1,2,3, Bolf EL1,3,4, Gordon JA1,2,3, Tye CE1,2,3, Boyd JR1,2,3, Tracy KM1,2,3, Nickerson JA8, van Wijnen AJ9, Imbalzano AN10, Heath JL1,2,3,11, Frietze SE5,6, Zaidi SK1,2,3, Carr FE1,3,4, Lian JB1,2,3, Stein JL1,2,3, Stein GS1,2,3.

Author information

1
Larner College of Medicine, University of Vermont, Burlington, Vermont.
2
Department of Biochemistry, University of Vermont, Burlington, Vermont.
3
University of Vermont Cancer Center, Burlington, Vermont.
4
Department of Pharmacology, University of Vermont College of Medicine, Burlington, Vermont.
5
Cellular Molecular Biomedical Sciences Program, University of Vermont, Burlington, Vermont.
6
Department of Biomedical and Health Sciences, University of Vermont, Burlington, Vermont.
7
Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.
8
Division of Genes and Development of the Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts.
9
Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic Minnesota, Rochester, Minnesota.
10
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts.
11
Department of Pediatrics, University of Vermont, Burlington, Vermont.

Abstract

Cells establish and sustain structural and functional integrity of the genome to support cellular identity and prevent malignant transformation. In this review, we present a strategic overview of epigenetic regulatory mechanisms including histone modifications and higher order chromatin organization (HCO) that are perturbed in breast cancer onset and progression. Implications for dysfunctions that occur in hormone regulation, cell cycle control, and mitotic bookmarking in breast cancer are considered, with an emphasis on epithelial-to-mesenchymal transition and cancer stem cell activities. The architectural organization of regulatory machinery is addressed within the contexts of translating cancer-compromised genomic organization to advances in breast cancer risk assessment, diagnosis, prognosis, and identification of novel therapeutic targets with high specificity and minimal off target effects.

KEYWORDS:

RUNX; breast cancer; cancer stem cells; epithelial to mesenchymal transition; higher order chromatin organization; hormone regulation; mitotic bookmarking

PMID:
30873710
DOI:
10.1002/gcc.22731

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