The role of chromatin, microRNAs, and tumor stem cells in ovarian cancer

Issue title: Biomarkers for Ovarian Cancer: New Technologies and Targets to Address Persistently Unmet Needs

Guest editors: Michael A. Tainskyx and Anna Lokshiny

Article type: Research Article

Authors: Balch, Curtis^{a; b} | Nephew, Kenneth P.^{a; b; c; d; *}

Affiliations: [a] Medical Sciences, Indiana University School of Medicine, Bloomington, IN, USA | [b] Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA | [c] Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA | [d] Department of Obstetrics and Gynecology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA | [x] Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI, USA | [y] University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA, USA

Correspondence: [*] Corresponding author: Professor Kenneth P. Nephew, Medical Sciences Program, Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Jordan Hall 302; 1001 East Third Street, Bloomington, IN 47408, USA. E-mail: [email protected].

Abstract: The term “epigenetics” refers to DNA sequence-independent events that regulate gene expression, including DNA methylation, modifications to histone proteins, and microRNA-associated post-transcriptional control of protein translation. Epigenetic aberrations are now considered a defining characteristic of numerous human pathologies, including cancer. However, in contrast to DNA sequence mutations, many oncogenic epigenetic modifications are potentially reversible, with studies now showing numerous tumor cell types to possess remarkable phenotypic “plasticity,” strongly supporting possible reversion of their malignant status. The “epigenome” of one such malignancy, ovarian cancer, has now been studied in depth, with specific epigenetic alterations correlated with tumor initiation, progression, metastasis, and therapy resistance. Ovarian cancer is the most lethal malignancy of the female reproductive tract, largely due to lack or diagnoses of early-stage disease and the eventual develoment of drug resistance; thus, reliable early detection biomarkers and alternative therapies are urgently needed. In this chapter, we discuss the epigenetics of ovarian cancer, including its likely role in the establishment of “cancer stem cells,” i.e., highly tumorigenic progenitor cells believed to be largely or solely responsible for the propagation of malignant, chemotherapy-resistant and metastatic disease. Improved understanding of these gene-regulatory phenomena could likely result in improved detection and survival of this highly destructive malignancy.

DOI: 10.3233/CBM-2011-0214

Journal: Cancer Biomarkers, vol. 8, no. 4-5, pp. 203-221, 2011