Corruption of the intra-gene DNA methylation architecture is a hallmark of cancer.
Corruption of the intra-gene DNA methylation architecture is a hallmark of cancer.
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DOI：
10.1371/journal.pone.0068285
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Widschwendter M
中科院分区：
文献类型：
--
作者：
Bartlett TE;Zaikin A;Olhede SC;West J;Teschendorff AE;Widschwendter M
表观遗传过程-包括DNA甲基化-越来越多地被视为在癌症等慢性疾病中发挥重要作用。众所周知，特定基因或位点的甲基化水平在正常组织和患病组织之间不同。在这里，我们调查是否基因内甲基化结构在癌症中被破坏，以及是否在一个定义的基因内的单个CpG的甲基化水平的变化能够区分癌组织和正常组织，并与异质性肿瘤表型，如基因表达所定义的。我们分析了270985个CpG注释到18272个基因，在3284癌和681正常样本，对应于14种不同的癌症类型。在这样做的过程中，我们发现了不同表型的基因内甲基化模式的新差异，特别是在那些对干细胞生物学至关重要的基因中;我们对基因内甲基化结构的测量是比仅基于平均甲基化水平的测量更好的表型决定因素（所有14种测试疾病的K-S检验）。与常规的每CpG β值相比，这些每基因甲基化测量也代表了复杂性的显著降低。我们的研究结果强烈支持这样的观点，即基因内甲基化结构对于开发基于DNA的癌症生物标志物具有巨大的临床潜力。
Epigenetic processes - including DNA methylation - are increasingly seen as having a fundamental role in chronic diseases like cancer. It is well known that methylation levels at particular genes or loci differ between normal and diseased tissue. Here we investigate whether the intra-gene methylation architecture is corrupted in cancer and whether the variability of levels of methylation of individual CpGs within a defined gene is able to discriminate cancerous from normal tissue, and is associated with heterogeneous tumour phenotype, as defined by gene expression. We analysed 270985 CpGs annotated to 18272 genes, in 3284 cancerous and 681 normal samples, corresponding to 14 different cancer types. In doing so, we found novel differences in intra-gene methylation pattern across phenotypes, particularly in those genes which are crucial for stem cell biology; our measures of intra-gene methylation architecture are a better determinant of phenotype than measures based on mean methylation level alone (K-S test in all 14 diseases tested). These per-gene methylation measures also represent a considerable reduction in complexity, compared to conventional per-CpG beta-values. Our findings strongly support the view that intra-gene methylation architecture has great clinical potential for the development of DNA-based cancer biomarkers.
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影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
影响因子：
30.8
作者：
Widschwendter, Martin;Fiegl, Heidi;Laird, Peter W.
通讯作者：
Laird, Peter W.
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
7
作者：
Easwaran, Hariharan;Johnstone, Sarah E.;Baylin, Stephen B.
通讯作者：
Baylin, Stephen B.
影响因子：
64.5
作者：
Lee, TI;Jenner, RG;Young, RA
通讯作者：
Young, RA