A genome-wide DNA methylation study in colorectal carcinoma.
A genome-wide DNA methylation study in colorectal carcinoma.
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DOI：
10.1186/1755-8794-4-50
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发表时间：
2011-06-23
影响因子：
2.7
通讯作者：
Ahsan H
中科院分区：
文献类型：
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作者：
Kibriya MG;Raza M;Jasmine F;Roy S;Paul-Brutus R;Rahaman R;Dodsworth C;Rakibuz-Zaman M;Kamal M;Ahsan H
我们对27,578个CpG位点进行了全基因组扫描，覆盖14,475个基因，以鉴定结直肠癌（CRC）中的差异甲基化位点（DML）。我们使用Illumina的Infinium甲基化试验，对从一家三级医疗中心连续诊断的24名患者的24个新鲜冷冻结直肠癌组织和相应的正常结肠组织中提取的成对DNA样本进行检测。在结直肠癌中共发现627个DML，覆盖513个基因，其中535个为新型DML，覆盖465个基因。我们还在相同样本的一个子集中，通过非亚硫酸盐转化q- pcr甲基化分析验证了Illumina Infinium顶级基因的甲基化数据。我们还进行了全基因组拷贝数和表达芯片的整合以及甲基化分析，以观察甲基化的功能影响。基因集富集分析（Gene Set Enrichment Analysis， GSEA）显示，CRC中发生高甲基化的主要“基因集”有“g蛋白信号抑制腺苷酸环化酶活性”、“Rac鸟苷核苷酸交换因子活性”、“维甲酸受体信号通路调控”和“雌激素受体活性”。两水平嵌套交叉验证表明，基于dml的预测模型可提供合理的灵敏度（约89%）、特异性（约95%）、阳性预测值（约95%）和阴性预测值（约89%），提示这些标志物可能具有潜在的临床应用价值。我们的CRC全基因组甲基化研究清楚地支持了大多数先前的发现；此外，我们在结直肠癌组织中发现了大量新的DML。如果在未来的研究中得到证实，这些发现可能会导致鉴定潜在临床应用的基因组标记。
We performed a genome-wide scan of 27,578 CpG loci covering 14,475 genes to identify differentially methylated loci (DML) in colorectal carcinoma (CRC). We used Illumina's Infinium methylation assay in paired DNA samples extracted from 24 fresh frozen CRC tissues and their corresponding normal colon tissues from 24 consecutive diagnosed patients at a tertiary medical center. We found a total of 627 DML in CRC covering 513 genes, of which 535 are novel DML covering 465 genes. We also validated the Illumina Infinium methylation data for top-ranking genes by non-bisulfite conversion q-PCR-based methyl profiler assay in a subset of the same samples. We also carried out integration of genome-wide copy number and expression microarray along with methylation profiling to see the functional effect of methylation. Gene Set Enrichment Analysis (GSEA) showed that among the major "gene sets" that are hypermethylated in CRC are the sets: "inhibition of adenylate cyclase activity by G-protein signaling", "Rac guanyl-nucleotide exchange factor activity", "regulation of retinoic acid receptor signaling pathway" and "estrogen receptor activity". Two-level nested cross validation showed that DML-based predictive models may offer reasonable sensitivity (around 89%), specificity (around 95%), positive predictive value (around 95%) and negative predictive value (around 89%), suggesting that these markers may have potential clinical application. Our genome-wide methylation study in CRC clearly supports most of the previous findings; additionally we found a large number of novel DML in CRC tissue. If confirmed in future studies, these findings may lead to identification of genomic markers for potential clinical application.
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影响因子：
3.7
作者：
Liu J;Morgan M;Hutchison K;Calhoun VD
通讯作者：
Calhoun VD
影响因子：
3.8
作者：
Ang PW;Loh M;Liem N;Lim PL;Grieu F;Vaithilingam A;Platell C;Yong WP;Iacopetta B;Soong R
通讯作者：
Soong R
影响因子：
24.5
作者：
Ogino, S.;Cantor, M.;Fuchs, C. S.
通讯作者：
Fuchs, C. S.
DOI：
10.1002/gcc.20699
发表时间：
2009-11
期刊：
Genes, chromosomes & cancer
影响因子：
--
作者：
Camps J;Nguyen QT;Padilla-Nash HM;Knutsen T;McNeil NE;Wangsa D;Hummon AB;Grade M;Ried T;Difilippantonio MJ
通讯作者：
Difilippantonio MJ
影响因子：
46.9
作者：
通讯作者：
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