DNA methylation profiles of female steroid hormone-driven human malignancies

Tumor DNA contains valuable clues about the origin and pathogenesis of human cancers. Alterations in DNA methylation can lead to silencing of genes associated with distinct tumorigenic pathways. These pathway-specific DNA methylation changes help define tumor-specific DNA methylation profiles that can be used to further our understanding of tumor development, as well as provide tools for molecular diagnosis and early detection of cancer. Female sex hormones have been implicated in the etiology of several of the women's cancers including breast, endometrial, ovarian, and proximal colon cancers. We have reviewed the DNA methylation profiles of these cancers to determine whether the hormonal regulation of these cancers results in specific DNA methylation alterations. Although subsets of tumors in each of these four types of cancers were found to share some DNA methylation alterations, we did not find evidence for global hormone-specific DNA methylation alterations, suggesting that female sex hormones may participate in different tumorigenic pathways that are associated with distinct DNA methylation-based molecular signatures. One such pathway may include MLH1 methylation in the context of the CpG island methylator phenotype.