Laboratory of Genetics and Epigenetics, de Duve Institute, Catholic University of Louvain, Brussels, Belgium.
Adv Exp Med Biol. 2013;754:149-66. doi: 10.1007/978-1-4419-9967-2_7.
DNA methylation, occurring at cytosines in CpG dinucleotides, is a potent mechanism of transcriptional repression. Proper genomic methylation -patterns become profoundly altered in cancer cells: both gains (hypermethylation) and losses (hypomethylation) of methylated sites are observed. Although DNA hypomethylation is detected in a vast majority of human tumors and affects many genomic regions, its role in tumor biology remains elusive. Surprisingly, DNA hypomethylation in cancer was found to cause the aberrant activation of only a limited group of genes. Most of these are normally expressed exclusively in germline cells and were grouped under the term "cancer-germline" (CG) genes. CG genes represent unique examples of genes that rely primarily on DNA methylation for their tissue-specific expression. They are also being exploited to uncover the mechanisms that lead to DNA hypomethylation in tumors. Moreover, as CG genes encode tumor-specific antigens, their activation in cancer highlights a direct link between epigenetic alterations and tumor immunity. As a result, clinical trials combining epigenetic drugs with anti-CG antigen vaccines are being considered.
DNA 甲基化发生在 CpG 二核苷酸中的胞嘧啶上，是一种有效的转录抑制机制。正常的基因组甲基化模式在癌细胞中发生了深刻的改变：观察到甲基化位点的增加（高甲基化）和减少（低甲基化）。尽管在绝大多数人类肿瘤中都检测到 DNA 低甲基化，并影响许多基因组区域，但它在肿瘤生物学中的作用仍不清楚。令人惊讶的是，在癌症中发现 DNA 低甲基化仅导致有限数量的基因异常激活。这些基因中的大多数通常仅在生殖细胞中表达，并被归为“癌症-生殖系”（CG）基因。CG 基因是主要依赖 DNA 甲基化来实现组织特异性表达的基因的独特例子。它们也被用来揭示导致肿瘤中 DNA 低甲基化的机制。此外，由于 CG 基因编码肿瘤特异性抗原，它们在癌症中的激活突出了表观遗传改变与肿瘤免疫之间的直接联系。因此，正在考虑将表观遗传药物与抗 CG 抗原疫苗联合用于临床试验。
