University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15232, USA.
Breast Cancer Res. 2011;13(6):225. doi: 10.1186/bcr2925. Epub 2011 Nov 1.
Epigenetic changes are critical for development and progression of cancers, including breast cancer. Significant progress has been made in the basic understanding of how various epigenetic changes such as DNA methylation, histone modification, miRNA expression, and higher order chromatin structure affect gene expression. The present review will focus on methylation and demethylation of histones. While the acetylation of histones has been at the forefront of well-characterized post-translational modifications of histones, including the development of inhibitors targeting de-acetylating enzymes, the past few years have witnessed a dramatic increase in knowledge regarding the role of histone methylation/demethylation. This is an exciting and rapidly evolving area of research, with much promise for potential clinical intervention in several cancers including breast cancer. We also summarize efforts to identity DNA methylation signatures that could be prognostic and/or predictive markers in breast cancer, focusing on recent studies using genome-wide approaches. Finally, we briefly review the efforts made by both the National Institutes of Health Epigenome Project and The Cancer Genome Atlas, especially highlighting the study of breast cancer epigenetics, exciting technological advances, potential roadblocks, and future directions.
表观遗传改变对于癌症的发生和发展至关重要，包括乳腺癌。在理解各种表观遗传改变（如 DNA 甲基化、组蛋白修饰、miRNA 表达和高级染色质结构）如何影响基因表达方面已经取得了重大进展。本综述将重点讨论组蛋白的甲基化和去甲基化。虽然组蛋白的乙酰化一直是研究得最透彻的组蛋白翻译后修饰之一，包括开发针对去乙酰化酶的抑制剂，但过去几年，人们对组蛋白甲基化/去甲基化的作用有了更深入的了解。这是一个令人兴奋且快速发展的研究领域，在包括乳腺癌在内的几种癌症的潜在临床干预方面具有很大的前景。我们还总结了鉴定可能在乳腺癌中具有预后和/或预测价值的 DNA 甲基化特征的努力，重点关注使用全基因组方法的最新研究。最后，我们简要回顾了美国国立卫生研究院表观基因组计划和癌症基因组图谱所做的努力，特别是强调了乳腺癌表观遗传学的研究、令人兴奋的技术进步、潜在的障碍和未来的方向。
