Integrated profiling reveals a global correlation between epigenetic and genetic alterations in mesothelioma.
Integrated profiling reveals a global correlation between epigenetic and genetic alterations in mesothelioma.
复制标题
DOI：
10.1158/0008-5472.can-10-0190
复制
发表时间：
2010-07-15
期刊：
影响因子：
11.2
通讯作者：
Kelsey KT
中科院分区：
文献类型：
--
作者：
Christensen BC;Houseman EA;Poage GM;Godleski JJ;Bueno R;Sugarbaker DJ;Wiencke JK;Nelson HH;Marsit CJ;Kelsey KT
间皮瘤的发展主要与石棉接触有关，但遗传和表观遗传改变的综合作用尚不清楚。我们在一系列胸膜间皮瘤病例 (n=23) 中研究了基因拷贝数 (CN) 改变与 DNA 甲基化谱之间的潜在关系。在所探测的位点上没有明显相关的 CN 改变和甲基化的实例，而对其相关基因的平均位点显示只有两个基因具有显着相关的 CN 和甲基化改变。与缺乏离散相关性相反，当比较甲基化谱类别之间的 CN 改变程度时，肿瘤 CN 改变的总体程度与 DNA 甲基化谱显着相关。此外，有证据表明这种关联部分归因于 DNA 甲基转移酶基因 DNMT1 普遍存在的等位基因丢失。我们的研究结果定义了间皮瘤中整体遗传和整体表观遗传失调之间的密切关联，而不是基因失活的离散、局部协调。
Development of mesothelioma is linked mainly to asbestos exposure but the combined contributions of genetic and epigenetic alterations are unclear. We investigated the potential relationships between gene copy number (CN) alterations and DNA methylation profiles in a case series of pleural mesotheliomas (n=23). There were no instances of significantly correlated CN alteration and methylation at probed loci, whereas averaging loci over their associated genes revealed only two genes with significantly correlated CN and methylation alterations. In contrast to the lack of discrete correlations, the overall extent of tumor CN alteration was significantly associated with DNA methylation profile when comparing CN alteration extent among methylation profile classes. Further, there was evidence that this association was partially attributable to prevalent allele loss at the DNA methyltransferase gene DNMT1. Our findings define a strong association between global genetic and global epigenetic dysregulation in mesothelioma, rather than a discrete, local coordination of gene inactivation.