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肝母细胞瘤组织中DNA甲基化的全基因组分析。

Genome-wide analysis of DNA methylation in hepatoblastoma tissues.

作者信息

Cui Ximao, Liu Baihui, Zheng Shan, Dong Kuiran, Dong Rui

机构信息

Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defects and Key Laboratory of Neonatal Diseases, Ministry of Health, Shanghai 201102, P.R. China.

出版信息

Oncol Lett. 2016 Aug;12(2):1529-1534. doi: 10.3892/ol.2016.4789. Epub 2016 Jun 28.

Abstract

DNA methylation has a crucial role in cancer biology. In the present study, a genome-wide analysis of DNA methylation in hepatoblastoma (HB) tissues was performed to verify differential methylation levels between HB and normal tissues. As alpha-fetoprotein (AFP) has a critical role in HB, methylation levels were also detected using pyrosequencing. Normal and HB liver tissue samples (frozen tissue) were obtained from patients with HB. Genome-wide analysis of DNA methylation in these tissues was performed using an Infinium HumanMethylation450 BeadChip, and the results were confirmed with reverse transcription-quantitative polymerase chain reaction. The Infinium HumanMethylation450 BeadChip demonstrated distinctively less methylation in HB tissues than in non-tumor tissues. In addition, methylation enrichment was observed in positions near the transcription start site of , which exhibited lower methylation levels in HB tissues than in non-tumor liver tissues. Lastly, a significant negative correlation was observed between messenger RNA expression and DNA methylation percentage, using linear Pearson's correlation coefficients. The present results demonstrate differential methylation levels between HB and normal tissues, and imply that aberrant methylation of in HB could reflect HB development. Expansion of these findings could provide useful insight into HB biology.

摘要

DNA甲基化在癌症生物学中起着至关重要的作用。在本研究中,对肝母细胞瘤(HB)组织中的DNA甲基化进行了全基因组分析,以验证HB组织与正常组织之间的甲基化水平差异。由于甲胎蛋白(AFP)在HB中起关键作用,还使用焦磷酸测序法检测了甲基化水平。从HB患者获取正常和HB肝组织样本(冷冻组织)。使用Infinium HumanMethylation450 BeadChip对这些组织中的DNA甲基化进行全基因组分析,结果通过逆转录定量聚合酶链反应得到证实。Infinium HumanMethylation450 BeadChip显示,HB组织中的甲基化明显少于非肿瘤组织。此外,在 转录起始位点附近的位置观察到甲基化富集,该位置在HB组织中的甲基化水平低于非肿瘤肝组织。最后,使用线性Pearson相关系数观察到信使RNA表达与DNA甲基化百分比之间存在显著负相关。本研究结果表明HB组织与正常组织之间存在甲基化水平差异,意味着HB中 的异常甲基化可能反映了HB的发展。这些发现的扩展可为HB生物学提供有用的见解。

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