DNA Hypomethylation and Activation of Germline-Specific Genes in Cancer
DNA Hypomethylation and Activation of Germline-Specific Genes in Cancer
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DOI：
10.1007/978-1-4419-9967-2_7
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发表时间：
2013-01-01
期刊：
影响因子：
--
通讯作者：
Loriot, Axelle
中科院分区：
文献类型：
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作者：
De Smet, Charles;Loriot, Axelle
DNA甲基化发生在CpG二核苷酸的胞嘧啶上，是转录抑制的一种有效机制。适当的基因组甲基化模式在癌细胞中发生了深刻的变化：观察到甲基化位点的获得(高甲基化)和丢失(低甲基化)。虽然DNA低甲基化在绝大多数人类肿瘤中被检测到，并影响到许多基因组区域，但它在肿瘤生物学中的作用仍然难以捉摸。令人惊讶的是，在癌症中发现DNA低甲基化只导致有限一组基因的异常激活。它们中的大多数通常只在生殖系细胞中表达，并被归类为“癌症-生殖系”(CG)基因。CG基因代表了主要依靠DNA甲基化进行组织特异性表达的基因的独特例子。它们还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变化和肿瘤免疫之间的直接联系。因此，将表观遗传药物与抗CG抗原疫苗相结合的临床试验正在考虑之中。
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.