High-resolution mapping of DNA hypermethylation and hypomethylation in lung cancer
High-resolution mapping of DNA hypermethylation and hypomethylation in lung cancer
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DOI：
10.1073/pnas.0710735105
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发表时间：
2008-01-08
影响因子：
11.1
通讯作者：
Pfeifer, Gerd P.
中科院分区：
文献类型：
--
作者：
Rauch, Tibor A.;Zhong, Xueyan;Pfeifer, Gerd P.
DNA甲基化模式的改变是人类癌症的一个重要特征。肿瘤的基因组DNA甲基化水平降低，并含有高甲基化的CpG岛，但DNA低甲基化和高甲基化的完整程度和序列背景尚不清楚。在这里，我们使用甲基化CpG岛恢复测定辅助高分辨率基因组切片和CpG岛阵列来分析肺鳞状细胞癌和匹配的正常肺组织的甲基化模式。来自不同个体的正常组织显示出总体上非常相似的DNA甲基化模式。每个肿瘤包含数百个高甲基化的CpG岛。我们在80-100%的SCC肿瘤中鉴定并确认了11个甲基化的CpG岛，其中许多岛有望成为肺癌早期检测的有效生物标志物。此外，我们发现肿瘤中广泛的DNA低甲基化特别发生在重复序列上，包括短和长穿插的核元件和LTR元件，片段复制和亚端粒区域，但单拷贝序列很少发生去甲基化。结果与人类癌症中重复DNA序列甲基化的特定缺陷一致。
Changes in DNA methylation patterns are an important characteristic of human cancer. Tumors have reduced levels of genomic DNA methylation and contain hypermethylated CpG islands, but the full extent and sequence context of DNA hypomethylation and hypermethylation is unknown. Here, we used methylated CpG island recovery assay-assisted high-resolution genomic tiling and CpG island arrays to analyze methylation patterns in lung squamous cell carcinomas and matched normal lung tissue. Normal tissues from different individuals showed overall very similar DNA methylation patterns. Each tumor contained several hundred hypermethylated CpG islands. We identified and confirmed 11 CpG islands that were methylated in 80-100% of the SCC tumors, and many hold promise as effective biomarkers for early detection of lung cancer. In addition, we find that extensive DNA hypomethylation in tumors occurs specifically at repetitive sequences, including short and long interspersed nuclear elements and LTR elements, segmental duplications, and subtelomeric regions, but single-copy sequences rarely become demethylated. The results are consistent with a specific defect in methylation of repetitive DNA sequences in human cancer.