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.


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


  • Chromatin