文章：

DNA甲基化标记的力量和前景

The power and the promise of DNA methylation markers

原文发布日期：2003-04-01

DOI: 10.1038/nrc1045

类型: Review Article

开放获取: 否

要点：

1. Cytosine-5 DNA methylation occurs in mammals at CpG dinucleotides. About 70% of the CpG dinucleotides in the mammalian genome are methylated.
2. The complexity of varying distributions of methylated cytosines across the approximately 50 million CpG dinucleotides of each mammalian genome in a DNA sample that is derived from a heterogenous tissue sample is a diagnostic dream and an analytical nightmare.
3. A nomenclature for the three principal approaches to methylation analysis — methylation content, methylation levels and methylation patterns — is proposed. The latter two types of analysis can be performed at multiple sites in the genome to yield methylation profiles.
4. In the past decade, DNA methylation analysis has been revolutionized by two technological advances — bisulphite modification of DNA and methylation-specific polymerase chain reaction (MSP).
5. CpG islands are approximately 1-kb stretches of DNA-containing clusters of CpG dinucleotides that are usually unmethylated in normal cells and are often located near the 5′ ends of genes. Methylation of promoter CpG islands is associated with a closed chromatin structure and transcriptional silencing of the associated gene.
6. Hypermethylation of CpG islands is a common event in carcinogenesis. The transcriptional silencing of tumour-suppressor genes by promoter CpG island hypermethylation can contribute to oncogenesis.
7. DNA methylation profiles represent a more chemically and biologically stable source of molecular diagnostic information than RNA or most proteins. The diagnostic potential of DNA methylation profiles is still largely untapped.
8. Cancer-specific DNA methylation patterns can be detected in tumour-derived free DNA in the bloodstream and in epithelial tumour cells shed into the lumen, offering a promising approach to the early detection of cancer. Clinical application will first require further validation and will ultimately be based on standardized MSP-based technologies, such as MethyLight, rather than on gel-based techniques.
9. A distinction between the clinical and analytical sensitivities of DNA methylation biomarkers is proposed.

要点翻译：

1. 胞嘧啶-5 DNA甲基化发生于哺乳动物的CpG二核苷酸位点。哺乳动物基因组中约70%的CpG二核苷酸处于甲基化状态。
2. 在源自异质性组织样本的DNA中，每个哺乳动物基因组约5000万个CpG二核苷酸位点呈现不同的甲基化胞嘧啶分布，这种复杂的分布模式既是诊断学的理想靶点，也是分析技术的巨大挑战。
3. 本文提出甲基化分析的三种主要方法学术语：甲基化含量、甲基化水平和甲基化模式。后两种分析可在基因组多位点进行，从而获得甲基化谱。
4. 过去十年间，DNA甲基化分析技术因两大突破而革新——DNA亚硫酸氢盐修饰和甲基化特异性聚合酶链式反应（MSP）。
5. CpG岛是长约1kb、富含CpG二核苷酸簇的DNA区域，在正常细胞中通常处于非甲基化状态，且常位于基因5′端。启动子区CpG岛的甲基化与染色质结构关闭及相应基因的转录沉默相关。
6. CpG岛过度甲基化是致癌过程中的常见事件。启动子区CpG岛过度甲基化导致的肿瘤抑制基因转录沉默可促进肿瘤发生。
7. 与RNA或大多数蛋白质相比，DNA甲基化谱作为分子诊断信息源具有更高的化学稳定性和生物学稳定性。DNA甲基化谱的诊断潜力目前尚未被充分挖掘。
8. 癌症特异性DNA甲基化模式可在血液中肿瘤源性游离DNA及脱落到管腔的上皮肿瘤细胞中检测到，这为癌症早期检测提供了新途径。临床应用仍需进一步验证，并最终将基于标准化MSP技术（如MethyLight），而非凝胶检测技术。
9. 建议区分DNA甲基化生物标志物的临床灵敏度与分析灵敏度。

英文摘要：

The past few years have seen an explosion of interest in the epigenetics of cancer. This has been a consequence of both the exciting coalescence of the chromatin and DNA methylation fields, and the realization that DNA methylation changes are involved in human malignancies. The ubiquity of DNA methylation changes has opened the way to a host of innovative diagnostic and therapeutic strategies. Recent advances attest to the great promise of DNA methylation markers as powerful future tools in the clinic.

摘要翻译： 

过去几年，癌症表观遗传学的研究兴趣激增。这既源于染色质与DNA甲基化领域的激动人心的融合，也源于人们意识到DNA甲基化变化参与了人类恶性肿瘤的发生。DNA甲基化变化的普遍性为一系列创新诊断和治疗策略铺平了道路。最新进展证明，DNA甲基化标记作为未来临床中的强大工具具有巨大前景。

原文链接：

The power and the promise of DNA methylation markers