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

A J Fritz; N E Gillis; D L Gerrard; P D Rodriguez; D Hong; J T Rose; P N Ghule; E L Bolf; J A Gordon; C E Tye; J R Boyd; K M Tracy; J A Nickerson; A J van Wijnen; A N Imbalzano; J L Heath; S E Frietze; S K Zaidi; F E Carr; J B Lian; J L Stein; G S Stein

doi:10.1002/gcc.22731

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

Genes Chromosomes Cancer. 2019 Jul;58(7):484-499. doi: 10.1002/gcc.22731. Epub 2019 Mar 15.

Authors

A J Fritz^{1

2}, N E Gillis^{2

3}, D L Gerrard^{4

5}, P D Rodriguez^{4

5}, D Hong⁶, J T Rose^{1

2}, P N Ghule^{1

2}, E L Bolf^{2

3}, J A Gordon^{1

2}, C E Tye^{1

2}, J R Boyd^{1

2}, K M Tracy^{1

2}, J A Nickerson⁷, A J van Wijnen⁸, A N Imbalzano⁹, J L Heath^{1

2

10}, S E Frietze^{4

5}, S K Zaidi^{1

2}, F E Carr^{1

2

3}, J B Lian^{1

2}, J L Stein^{1

2}, G S Stein^{1

2}

Affiliations

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

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Breast Neoplasms / genetics*
Breast Neoplasms / prevention & control*
Cell Line, Tumor
Chromatin / genetics*
Epigenesis, Genetic / genetics*
Epithelial-Mesenchymal Transition / genetics
Female
Genome / genetics*
Humans
Mice
Neoplastic Stem Cells

Substances

Chromatin

Abstract

Publication types

MeSH terms

Substances

Grants and funding