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首页> 外文期刊>Seminars in cancer biology >DNA methylation patterns in lung carcinomas.
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DNA methylation patterns in lung carcinomas.

机译：肺癌中的DNA甲基化模式。

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摘要

The genome of epithelial tumors is characterized by numerous chromosomal aberrations, DNA base sequence changes, and epigenetic abnormalities. The epigenome of cancer cells has been most commonly studied at the level of DNA CpG methylation. In squamous cell carcinomas of the lung, CpG methylation patterns undergo substantial changes relative to normal lung epithelium. Using a genome-scale mapping technique for CpG methylation (MIRA-chip), we characterized CpG island methylation and methylation patterns of entire chromosome arms at a level of resolution of approximately 100 bp. In individual stage I lung carcinomas, several hundred and probably up to a thousand CpG islands become methylated. Interestingly, a large fraction (almost 80%) of the tumor-specifically methylated sequences are targets of the Polycomb complex in embryonic stem cells. Homeobox genes are particularly overrepresented and all four HOX gene loci on chromosomes 2, 7, 12, and 17 are hotspots for tumor-associated methylation because of the presence of multiple methylated CpG islands within these loci. DNA hypomethylation at CpGs in squamous cell tumors preferentially affects repetitive sequence classes including SINEs, LINEs, subtelomeric repeats, and segmental duplications. Since these epigenetic changes are found in early stage tumors, their contribution to tumor etiology as well as their potential usefulness as diagnostic or prognostic biomarkers of the disease should be considered.
机译：上皮肿瘤的基因组的特征在于众多的染色体畸变，DNA碱基序列变化和表观遗传异常。在DNA CpG甲基化水平上最常研究癌细胞的表观基因组。在肺鳞状细胞癌中，相对于正常肺上皮，CpG甲基化模式发生实质性变化。使用基因组规模的CpG甲基化图谱技术（MIRA芯片），我们以大约100 bp的分辨率表征了整个染色体臂的CpG岛甲基化和甲基化模式。在个别的I期肺癌中，数百个（可能多达一千个）CpG岛被甲基化。有趣的是，大部分肿瘤特异性甲基化序列（几乎80％）是胚胎干细胞中Polycomb复合物的靶标。同源异型框基因特别被代表，并且由于这些基因位点中存在多个甲基化的CpG岛，染色体2、7、12和17上的所有四个HOX基因位点都是与肿瘤相关的甲基化的热点。鳞状细胞肿瘤中CpG处的DNA低甲基化优先影响重复序列类别，包括SINE，LINE，亚端粒重复序列和节段重复。由于这些表观遗传学变化是在早期肿瘤中发现的，因此应考虑它们对肿瘤病因的贡献以及作为疾病诊断或预后生物标志物的潜在用途。

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