Department of Surgery, University of Washington, Box 356410, 1959 NE Pacific Street, Seattle, WA 98195, USA.
Nat Rev Gastroenterol Hepatol. 2011 Oct 18;8(12):686-700. doi: 10.1038/nrgastro.2011.173.
Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. It results from an accumulation of genetic and epigenetic changes in colon epithelial cells, which transforms them into adenocarcinomas. Over the past decade, major advances have been made in understanding cancer epigenetics, particularly regarding aberrant DNA methylation. Assessment of the colon cancer epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has hundreds to thousands of abnormally methylated genes. As with gene mutations in the cancer genome, a subset of these methylated genes, called driver genes, is presumed to have a functional role in CRC. The assessment of methylated genes in CRCs has also revealed a unique molecular subgroup of CRCs called CpG island methylator phenotype (CIMP) cancers; these tumors have a particularly high frequency of methylated genes. These advances in our understanding of aberrant methylation in CRC have led to epigenetic 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。它是由结肠上皮细胞中遗传和表观遗传变化的积累导致的,这些变化将它们转化为腺癌。在过去的十年中,人们在理解癌症表观遗传学方面取得了重大进展,特别是在异常 DNA 甲基化方面。对结肠癌表观基因组的评估表明,几乎所有 CRC 都有异常甲基化的基因,并且平均 CRC 甲基组有数百到数千个异常甲基化的基因。与癌症基因组中的基因突变一样,这些甲基化基因中的一部分,称为驱动基因,被认为在 CRC 中具有功能作用。CRC 中甲基化基因的评估还揭示了一种称为 CpG 岛甲基化表型(CIMP)癌症的 CRC 独特分子亚群;这些肿瘤具有特别高频率的甲基化基因。我们对 CRC 中异常甲基化的理解的这些进展导致了表观遗传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,这些表观遗传改变将在不久的将来被广泛用于指导 CRC 的预防和治疗。