Aberrant DNA Methylation Patterns in Gynecologic Cancers: Implications for Prevention and Therapy

Alterations in DNA methylation contribute to gynecologic cancers by affecting the expression of genes essential for normal homeostasis, hence providing a source for biomarkers. The reversible nature of DNA methylation also opens therapeutic options; yet, in breast, cervical, endometrial, and ovarian cancers, benefits from such treatments remain elusive. Genome-wide studies have revealed a plethora of genes with altered DNA methylation that far exceeds the number of genes that would bring tumor growth advantage. Such widespread alterations likely reflect the global reorganization of chromatin, including the heterochromatin compartment linked the lamina where DNA methylation is predominant. Moreover, gynecologic cancers possess distinct nuclear morphologies illustrated by shape and size and the expression of structural nuclear proteins lamin A/C that enable pathological subclassification and assessment of aggressiveness. Emerging evidence of a relationship between DNA methylation, chromatin compaction, and nuclear morphometry suggests reconsidering the use of epigenetic drugs by taking into account nuclear morphology.