Satellite DNA hypomethylation in karyotyped Wilms tumors
Satellite DNA hypomethylation in karyotyped Wilms tumors
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DOI：
10.1016/s0165-4608(02)00668-4
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发表时间：
2003-03-01
影响因子：
--
通讯作者：
Sawyer, J
中科院分区：
文献类型：
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作者：
Ehrlich, M;Hopkins, NE;Sawyer, J
以前，在1号染色体上的着丝粒周围卫星DNA的异常长区域中，发现高百分比的肾母细胞瘤是低甲基化的。我们现在表明，这些儿科癌症也经常在整个基因组的着丝粒卫星DNA低甲基化，并比较卫星DNA低甲基化与染色体重排。相对于正常体细胞组织，83%的肿瘤在着丝粒卫星α DNA中低甲基化。这通过在低严格条件下用CpG甲基化敏感性限制性内切酶消化后的印迹杂交来评估。用不同的酶得到了类似的结果，表明着丝粒DNA的普遍低甲基化。在51%的肿瘤中观察到另一个异染色质序列，1号染色体的着丝粒卫星2 DNA的低甲基化。通过细胞遗传学分析，染色体I的着丝粒或近着丝粒异染色质重排是最常见的结构畸变，见于14%的肿瘤。具有这种重排的肿瘤在着丝粒周围区域具有卫星DNA的低甲基化。这些结果表明，在癌症中，DNA低甲基化高度靶向于着丝粒和非着丝粒卫星DNA序列，并且与卫星DNA低甲基化导致癌症中核型不稳定性但不足以导致癌症中核型不稳定性并且可能在致癌作用中发挥其他作用一致。(C)2003年爱思唯尔科学公司All rights reserved.
Previously, a high percentage of Wilms tumors was found to be hypomethylated in the unusually long region of pericentromeric satellite DNA on chromosome 1. We now show that these pediatric cancers are also frequently hypomethylated in centromeric satellite DNA throughout the genome and compare satellite DNA hypomethylation with chromosome rearrangements. Relative to normal somatic tissues, 83% of the tumors were hypomethylated in centromeric satellite alpha DNA. This was assessed by blot hybridization under low-stringency conditions after digestion with CpG methylation-sensitive restriction endonucleases. Similar results were obtained with different enzymes, indicating generalized hypomethylation of centromeric DNA. Hypomethylation of another heterochromatic sequence, juxtacentromeric satellite 2 DNA of chromosome 1, was observed in 51% of the tumors. By cytogenetic analysis, rearrangements in the centromeric or juxtacentromeric heterochromatin of chromosome I were the most frequent structural aberration and were seen in 14% of the tumors. Tumors with such rearrangements had hypomethylation of satellite DNA in the pericentromeric region. These results show a high degree of targeting of DNA hypomethylation to centromeric and juxtacentromeric satellite DNA sequences in cancer and are consistent with satellite DNA hypomethylation contributing to, but not sufficing for, karyotypic instability in cancer and possibly playing other roles in carcinogenesis. (C) 2003 Elsevier Science Inc. All rights reserved.