DNA Methylation and Breast Cancer

Traditionally, scientists have focused on structural changes in DNA sequences, such as mutations and deletions, as the cause for altered patterns of gene expression in human cancer. However, a recent explosion of studies indicates that epigenetic changes can be equally important in controlling gene expression. For example, global changes in DNA methylation occur during the progression of breast cancer. These changes include hypomethylation and hypermethylation of chromosomal regions and specific genes that are implicated in the genesis of breast cancer. As an example, we will pay particular attention to two genes, estrogen and progesterone receptor, which have long been associated with breast cancer initiation and progression. Identifying and characterizing these epigenetic modifications may lead to improvements in early detection, prognosis and design of novel therapies for a disease that is one of the leading causes of cancer death among women. This review will describe the changes in DNA methylation that have been identified in breast cancer thus far, and their functional consequences, including gene silencing, uncontrolled cell growth, genomic instability and hypermutability. Further, we will discuss the clinical ramifications of these findings.