Epigenomics of breast cancer

Abstract

Breast cancer is the second most common malignant cancer and accounts for 1.38 million of the total new cancer cases and 458,400 of the total cancer deaths reported in 2008. Breast cancer with several subtypes is an extremely heterogeneous disease caused by interaction of both genetic and environmental risk factors. In order to understand the etiology of this heterogeneity, new perspectives like epigenetics are needed. The term epigenetics was coined by Conrad Hal Waddington in the early 1940s. It refers to the study of gene function and regulation alterations without changes in the DNA sequence of the genome. The main epigenetic modifications are DNA methylation, histone modifications, and small noncoding RNAs (miRNAs). DNA methylation is the first to be associated with cancer and the most widely studied among epigenetic modifications. It regulates the gene expression by modifying the accessibility of DNA to the transcriptional machinery. The importance of histone modification has been realized during the last 10 years, after identification of the coexistence of histone modifications. From the dynamically changing pattern of histone modification has emerged a new concept termed histone cross talk. The epigenetic modifications are faster and reversible than mutation and easily affected by aging, environmental stimuli, and food in heritable manner. These characteristics provide a vital position in the etiology of diseases. After several investigations, it is well understood that the epigenetic modifications are involved in not only many biological processes such as X-chromosome inactivation, genomic imprinting, RNA interference, and programming of the genome but also several disease like breast cancer. Today we realize that the accumulation of epigenetic modifications occurs in the development of breast cancer. In addition, the epigenetic modifications improve our knowledge about the biology and heterogeneity of breast cancer by large-scale methods. Therefore, the researchers focused on epigenetic alterations-based breast cancer therapy, and it is speculated that epigenetic modifications may be markers for breast cancer. It is likely that epigenetics-based therapy will become a reality in the near future.