Imprinting and Cancer Group, Epigenetics and Cancer Biology Program, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet de Llobregat, 08907, Barcelona, Spain.
Brief Funct Genomics. 2010 Jul;9(4):329-39. doi: 10.1093/bfgp/elq013. Epub 2010 Jun 15.
Genetic events alone cannot explain the entire process of carcinogenesis. It is estimated that there are more epigenetic alterations in cancer than DNA mutations, and disiphering driver and secondary events is essential to understand early processes of tumorigenesis. Epigenetic modifications control gene activity, governing whether a gene is transcribed or silent. In cancer, global patterns of two epigenetic marks, histone modifications and DNA methylation, are known to be extensively deregulated. Tumour cells are also characterized by loss-of-imprinting, a key epigenetic developmental mechanism. Genomic imprinting is the parent-of-origin, monoallelic expression of genes and is controlled by differentially DNA-methylated regions and allelic-histone modifications. With specific emphasis on imprinted loci this review will discuss alterations in DNA methylation and histone modifications in cancer. The recent advances in technology that might facilitate the identification and characterization of the epigenetic profiles of cancer will also be described.
遗传事件本身并不能解释癌症发生的整个过程。据估计,癌症中存在的表观遗传改变比 DNA 突变多,区分驱动事件和次要事件对于理解肿瘤发生的早期过程至关重要。表观遗传修饰控制基因活性,决定基因是转录还是沉默。在癌症中,两种表观遗传标记(组蛋白修饰和 DNA 甲基化)的全局模式已知广泛失调。肿瘤细胞还表现出印迹丢失,这是一种关键的表观遗传发育机制。基因组印迹是指基因的亲本来源、单等位基因表达,由差异 DNA 甲基化区域和等位基因组蛋白修饰控制。本文特别强调印迹基因座,将讨论癌症中 DNA 甲基化和组蛋白修饰的改变。还将描述最近在技术上的进步,这些进步可能有助于确定和描述癌症的表观遗传特征。