Epigenetics and Breast Cancer

The term epigenetic was introduced by Conard Waddington in 1942 as a concept of environmental influence in inducing phenotype modification. His work on developmental plasticity states that the environmental influences during development could induce alternative phenotypes from one genotype, one of the clearest examples is polyphenisms in insects. He showed that exposing the pupae of wild type Drosophila melanogaster to heat shock treatment, results in altered wing vein patterns (Waddington, 1952;Waddington, 1959a). Breeding individuals who have been exposed to these environmentally induced changes led to a stable population exhibiting the phenotype without the environmental stimulus. As a result of Waddington’s observations of the dynamic interaction between genes and variation in the environment during the plastic phase of development, he described phenotype induction as genetic canalization. Canalization describes the robustness of phenotypes in response to perturbation (Waddington, 1959b;Waddington, 1961;Waddington & Robertson, 1966). The epigenome controls the genome in both normal and abnormal cellular processes and events (Szyf et al., 2008;Vaissiere et al., 2008). Epigenetic system includes DNA methylation and histone modification and non-coding RNAs, which work cooperatively to control gene expression. As a result, epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Global changes in the epigenetic landscape are a hallmark of cancer (Hanahan & Weinberg, 2000). Methylation of cytosine bases in DNA provides a layer of epigenetic control in many eukaryotes that has important implications for normal biology and disease. DNA methylation is a crucial epigenetic modification of the genome that is involved in regulating many cellular processes. These include embryonic development, transcription, chromatin structure, X-chromosome inactivation, genomic imprinting, and chromosome stability. Additionally, in 1975, DNA methylation was related to the process of X chromosome inactivation in females (Riggs, 1975). Since then, it has been used as a marker for gene silencing and extensively studied as an important mechanism of epigenetic control (Jaenisch & Bird, 2003). For instance, methylation of CpG islands within the imprinted gene promoters ensures transcriptional silencing of the associated parental allele (Nafee et al., 2008). Consistent with these important roles, a growing number of human diseases