Epigenetic alterations in the breast: Implications for breast cancer detection, prognosis and treatment

Abstract

Epigenetic alterations of the genome such as DNA promoter methylation and chromatin remodeling play an important role in tumorigenesis. Recent findings indicate epigenetic modifications as key factors in breast carcinogenesis. These modifications are quite appealing as targets for preventative care and therapeutics because of their potential for reversal. Future medical care for breast cancer patients will likely depend upon a better understanding of the roles epigenetic modifications play in carcinogenesis. Here, we discuss the importance of epigenetics in breast cancer detection, prognosis, and therapy with an emphasis on mechanisms and epigenetic contributions to field cancerization effects.

Figure 1

Proposed models for epigenetic long-term silencing of a gene. A. Active transcription of a gene is dependent on transcription factor (TF) binding. Upon removal of the TF through down-regulation, gene silencing or other means, down-regulation of the targeted gene occurs. In the absence of activating transcription factors, PcGs, HDACs, and DNMTs are recruited to the promoter and initiate long-term transcriptional repression. CpG sites adjacent to the promoter are then methylated (represented by filled circles) and eventually a heterochromatin state of long-term silencing is established. B. As in panel A transcription of a gene is dependent upon TF binding. In the absence of TF binding, PcG is recruited to a promoter and initiates long-term transcriptional repression through modification of histones. This can occur in the absence of CpG islands or methylation.