HOX gene clusters are hotspots of de novo methylation in CpG islands of human lung adenocarcinomas

HOX gene clusters are hotspots of de novo methylation in CpG islands of human lung adenocarcinomas
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DOI:
10.1038/sj.onc.1205453
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发表时间:
2002-05-16
期刊:
影响因子:
8
通讯作者:
Miyamoto, Y
Miyamoto, Y
中科院分区:
医学1区
文献类型:
--
作者:
Shiraishi, M;Sekiguchi, A;Miyamoto, Y

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CpG岛甲基化导致相关基因沉默,是肿瘤发生的重要步骤。在对人肺腺癌中甲基化的CpG岛进行全面分离后,我们发现在癌细胞中,新生CpG岛甲基化通常以零星的方式发生。然而,一些甲基化的CpG岛似乎聚集在离散的染色体区域。在这项研究中,我们研究了位于这些染色体位点的CpG岛的甲基化状态。我们发现在人肺腺癌中,许多位于HOXA和HOXD位点的CpG岛被甲基化。在患者肺组织非癌性部分的DNA中也观察到这些CpG岛的从头甲基化。这些结果表明存在对新生甲基化敏感的特定染色体区域。
CpG island methylation results in the silencing of the associated gene and is an important step in tumorigenesis. Following a comprehensive isolation of CpG islands that were methylated in human lung adenocarcinoma, we found that in cancer cells de novo CpG island methylation generally occurred in a sporadic manner. However, some methylated CpG islands appeared to cluster in discrete chromosomal regions. In this study, we have investigated the methylation status of CpG islands located at such chromosomal loci. We have found that many CpG islands at the HOXA and HOXD loci were methylated in human lung adenocarcinoma. The de novo methylation of these CpG islands was also observed in patient's DNA from noncancerous portions of lung tissue. These results indicate the presence of specific chromosomal regions that are susceptible to de novo methylation.