Okugawa Yoshinaga, Grady William M, Goel Ajay
Gastrointestinal Cancer Research Laboratory, Division of Gastroenterology, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Division of Gastroenterology, University of Washington School of Medicine, Seattle, Washington.
Gastroenterology. 2015 Oct;149(5):1204-1225.e12. doi: 10.1053/j.gastro.2015.07.011. Epub 2015 Jul 26.
Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. One of the fundamental processes driving the initiation and progression of CRC is the accumulation of a variety of genetic and epigenetic changes in colonic epithelial cells. Over the past decade, major advances have been made in our understanding of cancer epigenetics, particularly regarding aberrant DNA methylation, microRNA (miRNA) and noncoding RNA deregulation, and alterations in histone modification states. Assessment of the colon cancer "epigenome" has revealed that virtually all CRCs have aberrantly methylated genes and altered miRNA expression. The average CRC methylome has hundreds to thousands of abnormally methylated genes and dozens of altered miRNAs. As with gene mutations in the cancer genome, a subset of these epigenetic alterations, called driver events, are presumed to have a functional role in CRC. In addition, the advances in our understanding of epigenetic alterations in CRC have led to these alterations being developed as clinical biomarkers for diagnostic, prognostic, and therapeutic applications. Progress in this field suggests that these epigenetic alterations will be commonly used in the near future to direct the prevention and treatment of CRC.
结直肠癌(CRC)是全球癌症死亡的主要原因之一。驱动CRC发生和发展的一个基本过程是结肠上皮细胞中各种基因和表观遗传变化的积累。在过去十年中,我们对癌症表观遗传学的理解取得了重大进展,特别是在异常DNA甲基化、微小RNA(miRNA)和非编码RNA失调以及组蛋白修饰状态改变方面。对结肠癌“表观基因组”的评估表明,几乎所有的CRC都有异常甲基化的基因和改变的miRNA表达。平均而言,CRC甲基化组有数百到数千个异常甲基化的基因和数十个改变的miRNA。与癌症基因组中的基因突变一样,这些表观遗传改变的一个子集,称为驱动事件,被认为在CRC中具有功能作用。此外,我们对CRC表观遗传改变认识的进展导致这些改变被开发为用于诊断、预后和治疗应用的临床生物标志物。该领域的进展表明,这些表观遗传改变在不久的将来将被普遍用于指导CRC的预防和治疗。