Genome-wide DNA methylation profiling reveals novel epigenetically regulated genes and non-coding RNAs in human testicular cancer.
Genome-wide DNA methylation profiling reveals novel epigenetically regulated genes and non-coding RNAs in human testicular cancer.
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DOI：
10.1038/sj.bjc.6605505
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发表时间：
2010-01-19
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
睾丸生殖细胞瘤是年轻男性最常见的恶性肿瘤。尽管异常DNA甲基化与许多癌症的病理生理有关，但已知只有有限数量的基因在TGCT中发生表观遗传改变。本报告记录了在体外模型培养系统中差异甲基化的全基因组分析。在TGCT患者样本中验证了有趣的基因。在这项研究中，我们使用甲基化DNA免疫沉淀（MeDIP）和全基因组平铺阵列来鉴定差异甲基化区域（DMRs）。我们确定了35208个DMRs。然而，只有一小部分DMRs映射到启动子上。基因表达的全基因组分析揭示了一组受DNA甲基化调节的差异表达基因。我们发现了几个候选基因，包括APOLD1、PCDH10和RGAG1，它们在TGCT患者样本中出现了失调。令人惊讶的是，APOLD1先前被定位到TGCT易感位点12p13.1，这表明它可能在TGCT发病机制中很重要。我们还观察到一些非编码rna （ncRNAs）位点的甲基化异常。其中一种ncrna hsa-mir-199a在TGCT患者样本中下调，在我们的体外模型培养系统中也是如此。本报告首次应用medip芯片鉴定TGCT中的表观遗传调控基因和ncrna。我们还证明了基因间DMRs和内含子DMRs在调控ncRNAs中的作用。
Testicular germ cell tumour (TGCT) is the most common malignant tumour in young males. Although aberrant DNA methylation is implicated in the pathophysiology of many cancers, only a limited number of genes are known to be epigenetically changed in TGCT. This report documents the genome-wide analysis of differential methylation in an in vitro model culture system. Interesting genes were validated in TGCT patient samples. In this study, we used methylated DNA immunoprecipitation (MeDIP) and whole-genome tiling arrays to identify differentially methylated regions (DMRs). We identified 35 208 DMRs. However, only a small number of DMRs mapped to promoters. A genome-wide analysis of gene expression revealed a group of differentially expressed genes that were regulated by DNA methylation. We identified several candidate genes, including APOLD1, PCDH10 and RGAG1, which were dysregulated in TGCT patient samples. Surprisingly, APOLD1 had previously been mapped to the TGCT susceptibility locus at 12p13.1, suggesting that it may be important in TGCT pathogenesis. We also observed aberrant methylation in the loci of some non-coding RNAs (ncRNAs). One of the ncRNAs, hsa-mir-199a, was downregulated in TGCT patient samples, and also in our in vitro model culture system. This report is the first application of MeDIP-chip for identifying epigenetically regulated genes and ncRNAs in TGCT. We also demonstrated the function of intergenic and intronic DMRs in the regulation of ncRNAs.
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影响因子：
2.8
作者：
Andrews, PW
通讯作者：
Andrews, PW
影响因子：
3.5
作者：
Crockford, GP;Linger, R;Rapley, EA
通讯作者：
Rapley, EA
影响因子：
14.9
作者：
Carr, Ian M.;Valleley, Elizabeth M. A.;Bonthron, David T.
通讯作者：
Bonthron, David T.
广泛的表观遗传异常表明，人类精子异常的DNA甲基化缺陷。
影响因子：
3.7
作者：
Houshdaran S;Cortessis VK;Siegmund K;Yang A;Laird PW;Sokol RZ
通讯作者：
Sokol RZ
影响因子：
9.8
作者：
Illingworth R;Kerr A;Desousa D;Jørgensen H;Ellis P;Stalker J;Jackson D;Clee C;Plumb R;Rogers J;Humphray S;Cox T;Langford C;Bird A
通讯作者：
Bird A