文章：

基因启动子超甲基化作为肺癌的生物标志物

Gene-promoter hypermethylation as a biomarker in lung cancer

原文发布日期：2004-09-01

DOI: 10.1038/nrc1432

类型: Review Article

开放获取: 否

要点：

1. Lung cancer accounts for 30% of all deaths from cancer. Detection often occurs at an advanced stage and conventional chemotherapy is of limited effectiveness.
2. There is no validated screening approach for early detection of lung cancer. Spiral computed tomography and fluorescence bronchoscopy are being examined, but both might lack diagnostic sensitivity and specificity.
3. Epigenetic-mediated gene silencing in the form of aberrant promoter hypermethylation constitutes an alternative to coding-region mutation for loss of gene function.
4. Loss of gene transcription by promoter methylation is a crucial event in lung cancer initiation and progression. Genes involved in all aspects of normal cellular function are silenced by methylation.
5. The development of the methylation-specific PCR assay enabled the rapid identification of genes that are methylated in cancer. The high sensitivity and specificity of this assay also makes it feasible to detect gene methylation in biological fluids where heterogeneity exists between normal and premalignant/cancer cells.
6. The detection of gene-specific promoter methylation in sputum in people who developed squamous-cell lung cancer provided the first proof of concept that methylation changes could potentially be used as a molecular marker system in screening for early lung cancer.

要点翻译：

1. 肺癌占所有癌症致死病例的30%。确诊往往发生在晚期阶段，传统化疗效果有限。
2. 目前尚无经过验证的早期肺癌筛查方法。螺旋计算机断层扫描和荧光支气管镜检查正在研究中，但两者可能均缺乏诊断敏感性和特异性。
3. 表观遗传介导的基因沉默以异常启动子高甲基化的形式，构成了编码区突变之外导致基因功能丧失的另一种机制。
4. 启动子甲基化导致的基因转录失活是肺癌发生与发展中的关键事件。参与正常细胞功能各方面的基因均可通过甲基化作用陷入沉默。
5. 甲基化特异性PCR检测技术的发展使得快速识别癌症中发生甲基化的基因成为可能。该检测方法的高敏感性与特异性也使其能够在外观正常的细胞与癌前/癌细胞存在异质性的生物体液中检测基因甲基化。
6. 在罹患鳞状细胞肺癌患者的痰液中检测到基因特异性启动子甲基化，首次为"甲基化变化有望作为早期肺癌筛查的分子标记系统"这一概念提供了实证依据。

英文摘要：

Silencing of genes by aberrant promoter hypermethylation is now recognized as a crucial component in cancer initiation and progression. Highly sensitive assays have been developed to assess gene-promoter methylation in biological fluids. The detection of methylated genes in sputum could lead to the development of a screening test to non-invasively identify early cancer in high-risk people.

摘要翻译： 

基因启动子异常高甲基化导致的沉默现已被认为是癌症发生和进展中的关键环节。人们已开发出高灵敏度检测方法来评估生物体液中基因启动子的甲基化状态。在痰液中检测到甲基化基因有望促成一种筛查试验，用于无创性地在高风险人群中早期发现癌症。

原文链接：

Gene-promoter hypermethylation as a biomarker in lung cancer