DNA hypomethylation is prevalent even in low-grade breast cancers
DNA hypomethylation is prevalent even in low-grade breast cancers
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DOI：
10.4161/cbt.3.12.1222
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发表时间：
2004-12-01
影响因子：
3.6
通讯作者：
Ehrlich, M
中科院分区：
文献类型：
--
作者：
Jackson, K;Yu, MC;Ehrlich, M
基因组的某些部分的低甲基化和其他部分的高甲基化是人类癌症的非常常见的属性。我们以前表明，癌症相关的DNA低甲基化通常涉及卫星2（Sat2），1号染色体的大着丝粒（着丝粒相邻）异染色质的主要DNA成分。在这项研究中，我们比较了Sat2和着丝粒卫星DNA（Sat α）的甲基化，以及41个已知肿瘤分级和分期的乳腺腺癌，16个非肿瘤性乳腺组织（主要是纤维腺瘤）和各种正常体细胞组织对照的整体基因组甲基化。相对于纤维腺瘤或正常体细胞组织，癌症在Sat2处显著低甲基化，并且相对于正常体细胞组织，癌症在Sat α处显著低甲基化。然而，与Sat2不同，Sat α在癌症和非肿瘤性乳腺组织之间的甲基化没有显示出显著差异。因此，Sat2的低甲基化是比Sat α低甲基化更好的乳腺癌标志物。Sat2低甲基化与癌症中的整体DNA低甲基化显著相关，但与肿瘤分级、分期、腋窝淋巴结受累或激素受体状态无关。即使在1级或1期癌中，广泛的癌症相关的着丝粒卫星DNA低甲基化和整体DNA低甲基化也很常见，这表明基因组的去甲基化是乳腺癌发生的早期事件。
Hypomethylation of some portions of the genome and hypermethylation of others are very frequent attributes of human cancer. We previously showed that cancer-associated DNA hypomethylation often involves satellite 2 (Sat2), the main DNA component of the large juxtacentromeric (centromere-adjacent) heterochromatin of chromosome 1. In this study, we compared methylation of Sat2 and centromeric satellite DNA (Sat alpha) as well as overall genomic methylation in 41 breast adenocarinomas of known tumor grade and stage, 16 non-neoplastic breast tissues (mostly fibroadenomas), and a variety of normal somatic tissue controls. The cancers were significantly hypomethylated at Sat2 relative to the fibroadenomas or normal somatic tissues and at Sat alpha relative to the normal somatic tissues. However, unlike Sat2, Sat alpha did not display significant differences in methylation between the cancers and the non-neoplastic breast tissues. Therefore, hypomethylation at Sat2 is a much better marker of breast cancer than is Sat alpha hypomethylation. There was a significant association of Sat2 hypomethylation with global DNA hypomethylation in the cancers but not with tumor grade, stage, axillary lymph node involvement, or hormone receptor status. Extensive cancer-associated hypomethylation of juxtacentromeric satellite DNA and global DNA hypomethylation were common even in grade-1 or stage-1 carcinomas, which suggests that demethylation of the genome is an early event in breast carcinogenesis.