Center for Biomarker Research and Personalized Medicine, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.
Eur J Hum Genet. 2012 Sep;20(9):953-5. doi: 10.1038/ejhg.2012.33. Epub 2012 Feb 29.
DNA from Epstein-Barr virus-transformed lymphocyte cell lines (LCLs) has proven useful for studies of genetic sequence polymorphisms. Whether LCL DNA is suitable for methylation studies is less clear. We conduct a genome-wide methylation investigation using an array set with 45 million probes to investigate the methylome of LCL DNA and technical duplicates of WB DNA from the same 10 individuals. We focus specifically on methylation sites that show variation between individuals and, therefore, are potentially useful as biomarkers. The sample correlations for the methylation variable probes ranged from 0.69 to 0.78 for the WB duplicates and from 0.27 to 0.72 for WB vs LCL. To compare the pattern of the methylation signals, we grouped adjacent probes based on their inter-correlations. These analyses showed ∼29 000 and ∼14 000 blocks in WB and LCL, respectively. Merely 31% of the methylated regions detected in WB were detectable in LCLs. Furthermore, we observed significant differences in mean difference between WB and LCL as compared with duplicates of WB (P-value =2.2 × 10(-16)). Our study shows that there are substantial differences in the DNA methylation patterns between LCL and WB. Thus, LCL DNA should not be used as a proxy for WB DNA in methylome-wide studies.
来自 Epstein-Barr 病毒转化的淋巴细胞系 (LCL) 的 DNA 已被证明可用于研究遗传序列多态性。LCL DNA 是否适合甲基化研究则不太清楚。我们使用包含 4500 万个探针的阵列集进行了全基因组甲基化研究，以调查 10 个人的 LCL DNA 和相同个体的 WB DNA 的技术重复的甲基组。我们特别关注在个体之间显示出差异的甲基化位点，因此这些位点可能是有用的生物标志物。WB 重复样本的甲基化变量探针的样本相关性范围为 0.69 至 0.78，WB 与 LCL 的相关性范围为 0.27 至 0.72。为了比较甲基化信号的模式，我们根据它们的互相关将相邻的探针分组。这些分析表明，WB 和 LCL 中分别有 ∼29000 和 ∼14000 个块。在 LCL 中可检测到的 WB 中检测到的甲基化区域仅占 31%。此外，与 WB 的重复样本相比，我们观察到 WB 和 LCL 之间的平均差异存在显著差异（P 值 = 2.2×10(-16)）。我们的研究表明，LCL 和 WB 之间的 DNA 甲基化模式存在很大差异。因此，在全甲基化组研究中，不应将 LCL DNA 用作 WB DNA 的替代物。
