Epigenetic control of tumor suppression

Abstract

Epigenetic silencing of tumor suppressor genes is a major contributor to neoplastic transformation and is an area of intense research. Identification of genes that undergo cancer-specific CpG island hypermethylation in combination with repressive histone tail modifications (deacetylation and methylation) and correlation of these data with tumor stage, progression, and long-term prognosis are becoming increasingly common. The efforts directed toward elucidating the mechanisms of neoplastic tumor suppression catalyzed the convergence of epigenetics, chromatin remodeling, and pharmacology of epigenome-altering drugs. This review discusses the key findings and current concepts concerning the epigenetic control of tumor suppression and analyzes the role of DNA hypermethylation in conjunction with histone deacetylation and methylation profiles of tumor suppressor genes as it relates to epigenetic loss of function in malignancy. Examples arguing for hierarchic control and interdependent regulation within the cellular tumor suppression networks are also presented. Finally, the necessity of a human epigenome database integrating the continually produced experimental information for use by both researchers and clinicians for prospective translational multidisciplinary studies of tumor suppressor networks is rationalized.