Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Wiley Interdiscip Rev Syst Biol Med. 2010 Nov-Dec;2(6):654-69. doi: 10.1002/wsbm.89.
Epigenetics refers to heritable modifications of the genome that are not a result of changes in the DNA sequence and result in phenotypic changes. These changes can be stably transmitted through cell division and are potentially reversible. Epigenetic events are very important during normal development wherein a single progenitor cell proliferates and differentiates into various somatic cell types. This process occurs through modification of the genome without changing the genetic code. Because epigenetic control of gene expression is so important, aberrant epigenetic regulation can lead to disease and cancer. This article reviews epigenetic changes seen in cancer by examining epigenetic changes commonly found in multiple myeloma, a common hematologic malignancy of plasma cells. Epigenetic control of gene expression can be exerted by changes in DNA methylation, histone modifications, and expression of noncoding RNAs. Each of these regulatory mechanisms interacts with the others at different genomic locations and can be measured quantitatively within the cell, requiring that we consider these mechanisms not individually but as a biological system. DNA methylation was the earliest discovered epigenetic regulator and has been the focus of most investigations in cancer. We have thus focused on DNA methylation changes in the pathogenesis of multiple myeloma, which promises to become an excellent model for systems biological studies of epigenomic dysregulation in human disease.
表观遗传学是指基因组的可遗传修饰，这些修饰不是由于 DNA 序列的改变引起的，而是导致表型的变化。这些变化可以通过细胞分裂稳定地传递，并且具有潜在的可逆性。在正常发育过程中，表观遗传事件非常重要，在此过程中，单个祖细胞增殖并分化为各种体细胞类型。这个过程是通过基因组的修饰而不改变遗传密码来实现的。由于基因表达的表观遗传调控非常重要，异常的表观遗传调控可能导致疾病和癌症。本文通过检查多发性骨髓瘤中常见的表观遗传变化，综述了癌症中的表观遗传变化，多发性骨髓瘤是一种常见的浆细胞瘤血液恶性肿瘤。基因表达的表观遗传调控可以通过 DNA 甲基化、组蛋白修饰和非编码 RNA 的表达变化来实现。这些调控机制中的每一种都在不同的基因组位置与其他机制相互作用，可以在细胞内进行定量测量，这要求我们不仅要单独考虑这些机制，还要将它们视为一个生物系统。DNA 甲基化是最早发现的表观遗传调节剂，也是大多数癌症研究的重点。因此，我们专注于多发性骨髓瘤发病机制中的 DNA 甲基化变化，这有望成为人类疾病中表观基因组失调的系统生物学研究的一个极好模型。
