Global methylation profiling of lung cancer identifies novel methylated genes
Global methylation profiling of lung cancer identifies novel methylated genes
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DOI：
10.1038/sj.neo.7900162
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发表时间：
2001-07-01
期刊：
影响因子：
4.8
通讯作者：
Plass, C
中科院分区：
文献类型：
--
作者：
Dai, ZY;Lakshmanan, RR;Plass, C
表观遗传变化（包括 DNA 甲基化）是癌症中的常见现象。在肺癌中，胞嘧啶残基的甲基化可能以多种方式影响肿瘤的发生和进展，包括通过启动子甲基化沉默肿瘤抑制基因，以及为香烟烟雾燃烧产物中存在的多环芳烃形成加合物提供靶标。尽管异常 DNA 甲基化的重要性已广为人知，但肺癌中 DNA 甲基化的程度尚未确定。限制性地标基因组扫描 (RLGS) 是一种高度可重复的二维凝胶电泳，可在单个凝胶中确定多达 2000 个启动子序列的甲基化状态。我们选择了 1184 个 CpG 岛进行 RLGS 分析，并确定了它们在 16 种原发性非小细胞肺癌中的甲基化状态。一些肿瘤没有显示出甲基化，而其他肿瘤则在该图谱的所有 CpG 岛中显示出高达 5.3% 的甲基化。 21 个甲基化位点的克隆鉴定出 11 个基因和 6 个 EST。我们证明甲基化是原发性肿瘤和肺癌细胞系中 BMP3B 沉默过程的一部分。
Epigenetic changes, including DNA methylation, are a common finding in cancer. In lung cancers methylation of cytosine residues may affect tumor initiation and progression in several ways, including the silencing of tumor suppressor genes through promoter methylation and by providing the targets for adduct formation of polycyclic aromatic hydrocarbons present in combustion products of cigarette smoke. Although the importance of aberrant DNA methylation is well established, the extent of DNA methylation in lung cancers has never been determined. Restriction landmark genomic scanning (RLGS) is a highly reproducible two-dimensional gel electrophoresis that allows the determination of the methylation status of up to 2000 promoter sequences in a single gel. We selected 1184 CpG islands for RLGS analysis and determined their methylation status in 16 primary non-small cell lung cancers. Some tumors did not show methylation whereas others showed up to 5.3% methylation in all CpG islands of the profile. Cloning of 21 methylated loci identified 11 genes and 6 ESTs. We demonstrate that methylation is part of the silencing process of BMP3B in primary tumors and lung cancer cell lines.