Methylation profile of DNA repetitive elements in human testicular germ cell tumor

Methylation profile of DNA repetitive elements in human testicular germ cell tumor
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人睾丸生殖细胞肿瘤 DNA 重复元件的甲基化谱

DOI:
10.1002/mc.20831
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发表时间:
2011
期刊:
Mol Carcinog
影响因子:
--
通讯作者:
Okamoto K.
Okamoto K.
中科院分区:
--
文献类型:
--
作者:
Ushida H;Kawakami T;Minami K;Chano T;Okabe H;Okada Y;Okamoto K.

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睾丸生殖细胞肿瘤(TGCT)具有不同于其他类型癌症的独特表观遗传特征。为了进一步评价TGCTs的表观遗传学,本研究检测了TGCTs中DNA重复元件的DNA甲基化模式。采用亚硫酸氢盐基因组测序和联合亚硫酸氢盐限制性内切酶分析(COBRA)技术分析胚胎癌(EC)细胞系、原发性TGCT组织、TGCT旁非癌睾丸组织和体细胞癌细胞(睾丸恶性淋巴瘤组织和肾细胞癌细胞系)中DNA重复序列(LINE1和Alu重复序列)的甲基化模式。通过亚硫酸氢盐基因组测序和COBRA,LINE1在腺瘤性和非腺瘤性TGCT组织以及EC细胞系中广泛低甲基化。通过亚硫酸氢盐基因组测序,我们研究了位于E ‐ cadherin和XIST 5′端的两个Alu重复序列。这两个Alu元件在恶性肿瘤TGCT中广泛低甲基化,但在非恶性肿瘤TGCT中甲基化,包括两个EC衍生的细胞系。COBRA也观察到Alu重复序列在腺瘤性TGCT中的这种增加的非甲基化特征。虽然在体细胞组织来源的癌细胞中观察到DNA重复元件的部分去甲基化,但TGCT中的去甲基化程度比体细胞组织来源的癌细胞中更明显。我们观察到异常的去甲基化的DNA重复元件在一些组织邻近TGCT。结果表明,TGCT和体细胞组织来源的癌细胞之间发生或维持DNA重复序列去甲基化的潜在机制不同。© 2011 Wiley Periodicals,Inc.
Testicular germ cell tumors (TGCTs) have a unique epigenetic profile distinct from that of other types of cancer. To further evaluate epigenetics of TGCTs, this study examines DNA methylation patterns of DNA repetitive elements in TGCTs. Bisulfite genomic sequencing and combined bisulfite restriction analysis (COBRA) were used to analyze the methylation patterns of DNA repetitive elements (LINE1 and Alu repeats) in embryonal carcinoma (EC) derived cell lines, primary TGCT tissues, noncancerous testicular tissues adjacent to TGCTs and cancer cells derived from somatic tissues (testicular malignant lymphoma tissues and renal cell carcinoma cell lines). Through both bisulfite genomic sequencing and COBRA, LINE1 was extensively hypomethylated in both seminomatous and nonseminomatous TGCT tissues as well as EC cell lines. We studied two Alu repeats locating in the 5′ end ofE‐cadherinandXISTby bisulfite genomic sequencing. These two Alu elements were extensively hypomethylated in seminomatous TGCTs, but methylated in nonseminomatous TGCTs, including two EC derived cell lines. This increased unmethylated profile in seminomatous TGCTs was observed also by COBRA for Alu repeats. Although partial demethylation of DNA repetitive elements was observed in cancer cells of somatic tissue origin, the degree of demethylation was more pronounced in TGCTs than in cancer cells of somatic tissue origin. We observed abnormal demethylation of DNA repetitive elements in some of the tissues adjacent to TGCTs. The results indicate that the underlying mechanisms to undergo or maintain demethylation of DNA repetitive sequences differ between TGCTs and cancer cells of somatic tissue origin. © 2011 Wiley Periodicals, Inc.
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