Satellite DNA hypomethylation vs. overall genomic hypomethylation in ovarian epithelial tumors of different malignant potential
Satellite DNA hypomethylation vs. overall genomic hypomethylation in ovarian epithelial tumors of different malignant potential
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DOI：
10.1016/s0027-5107(98)00229-2
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发表时间：
1999-01-25
影响因子：
2.3
通讯作者：
Ehrlich, M
中科院分区：
文献类型：
--
作者：
Qu, GZ;Dubeau, L;Ehrlich, M
在许多类型的癌症中，包括卵巢上皮癌，在1号和16号染色体着丝粒附近的异染色质重排是常见的。卫星2 DNA是这些染色体着丝粒附近异常长的异染色质区域的主要序列。这些区域的重排和卫星2 DNA的低甲基化是一种罕见的隐性遗传病ICF(免疫缺陷、着丝粒区域不稳定和面部畸形)患者的特征。在所有出生后体细胞起源的正常组织中，卫星2 DNA高度甲基化。我们检测了不同恶性潜能的卵巢肿瘤，即卵巢囊腺瘤、低恶性潜能(LMP)肿瘤和上皮性癌中卫星2 DNA甲基化。大多数卵巢癌和LMP肿瘤在1号和16号染色体的卫星2 DNA上均表现为低甲基化。比较三种类型卵巢肿瘤中这些序列的甲基化，发现卫星DNA低甲基化的程度与卵巢肿瘤的恶性程度有统计学意义(P<；0.01)。此外，在这17种肿瘤中，全基因组的低甲基化和卫星2DNA的低甲基化之间也有统计学意义的关联(P<；0.005)。此外，我们还发现在许多此类肿瘤中，1号染色体着丝粒的卫星oc DNA发生了异常的低甲基化。我们的发现与假设一致，即全基因组低甲基化促进肿瘤发展的方式之一是它通常包括卫星低甲基化，这可能使细胞容易发生染色体结构和数量上的异常。一些与着丝粒周围异染色质结合的蛋白质对其靶序列的甲基化状态很敏感，因此可能是检测异常去甲基化和对染色体结构和稳定性的中介作用的传感器之一。(C)1999 Elsevier Science B.V.保留所有权利。
Rearrangements in heterochromatin in the vicinity of the centromeres of chromosomes 1 and 16 are frequent in many types of cancer, including ovarian epithelial carcinomas. Satellite 2 DNA is the main sequence in the unusually long heterochromatin region adjacent to the centromere of each of these chromosomes. Rearrangements in these regions and hypomethylation of satellite 2 DNA are a characteristic feature of patients with a rare recessive genetic disease, ICF (immunodeficiency, centromeric region instability, and facial anomalies). In all normal tissues of postnatal somatic origin, satellite 2 DNA is highly methylated. We examined satellite 2 DNA methylation in ovarian tumors of different malignant potential, namely, ovarian cystadenomas, low malignant potential (LMP) tumors, and epithelial carcinomas. Most of the carcinomas and LMP tumors exhibited hypomethylation in satellite 2 DNA of both chromosomes 1 and 16. A comparison of methylation of these sequences in the three types of ovarian neoplasms demonstrated that there was a statistically significant correlation between the extent of this satellite DNA hypomethylation and the degree of malignancy (P < 0.01). Also, there was a statistically significant association (P < 0.005) between genome-wide hypomethylation and undermethylation of satellite 2 DNA among these 17 tumors. In addition, we found abnormal hypomethylation of satellite oc DNA in the centromere of chromosome 1 in many of these tumors. Our findings are consistent with the hypothesis that one of the ways that genome-wide hypomethylation facilitates tumor development is that it often includes satellite hypomethylation which might predispose cells to structural and numerical chromosomal aberrations. Several of the proteins that bind to pericentromeric heterochromatin are known to be sensitive to the methylation status of their target sequences and so could be among the sensors for detecting abnormal demethylation and mediating effects on chromosome structure and stability. (C) 1999 Elsevier Science B.V. All rights reserved.