Epigenomic analysis of aberrantly methylated genes in colorectal cancer identifies genes commonly affected by epigenetic alterations.
Epigenomic analysis of aberrantly methylated genes in colorectal cancer identifies genes commonly affected by epigenetic alterations.
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DOI：
10.1245/s10434-011-1573-y
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发表时间：
2011-08
影响因子：
3.7
通讯作者：
Kim YS
中科院分区：
文献类型：
--
作者：
Kim YH;Lee HC;Kim SY;Yeom YI;Ryu KJ;Min BH;Kim DH;Son HJ;Rhee PL;Kim JJ;Rhee JC;Kim HC;Chun HK;Grady WM;Kim YS
确定结直肠癌（CRC）中常见甲基化异常基因的谱对于诊断和治疗应用具有重要价值。然而，对CRC中DNA甲基化模式的了解有限。我们使用基于微珠芯片的技术分析了结直肠癌和邻近正常粘膜中27，578个CpG位点的甲基化谱，这些位点跨越14，000多个基因。我们确定了621个位于启动子区域和CpG岛的CpG位点，与正常粘膜相比，CRC中的CpG位点显著高甲基化。18号染色体上的基因最常出现启动子高甲基化。根据基因本体论分析，受甲基化影响的最常见的生物学相关基因类别是与钙粘蛋白信号通路相关的类别。与全基因组表达阵列相比，mRNA表达更可能在显示启动子高甲基化的基因中下调，即使这在统计学上不显著。我们在使用焦磷酸测序的阵列研究中，与正常粘膜相比，验证了CRC中10个高甲基化的CpG位点（ADHFE1、BOLL、SLC6A15、ADAMTS5、TFPI 2、EYA 4、NPY、TWIST 1、LAMA 1、GAS 7）和2个低甲基化的CpG位点（MAEL、SFT 2D3）。通过焦磷酸测序测量的甲基化状态与甲基化阵列数据一致。基于微球芯片的甲基化谱是筛选结直肠癌异常甲基化基因的有效方法。此外，我们发现了新的甲基化基因，这些基因是CRC的候选诊断或预后标志物。
Determination of the profile of genes that are commonly methylated aberrantly in colorectal cancer (CRC) will have substantial value for diagnostic and therapeutic applications. However, there is limited knowledge of the DNA methylation pattern in CRC. We analyzed the methylation profile of 27,578 CpG sites spanning more than 14,000 genes in CRC and in the adjacent normal mucosa using beadchip array-based technology. We identified 621 CpG sites located in promoter regions and CpG islands that were significantly hypermethylated in CRC compared to normal mucosa. The genes on chromosome 18 showed promoter hypermethylation most frequently. According to gene ontology analysis, the most common biologically relevant class of genes affected by methylation was the class associated with the cadherin signaling pathway. Compared to the genome-wide expression array, mRNA expression was more likely to be down-regulated in the genes demonstrating promoter hypermethylation, even though this was not statistically significant. We validated 10 CpG sites that were hypermethylated (ADHFE1, BOLL, SLC6A15, ADAMTS5, TFPI2, EYA4, NPY, TWIST1, LAMA1, GAS7) and 2 CpG sites showing hypomethylation (MAEL, SFT2D3) in CRC compared to the normal mucosa in the array studies using pyrosequencing. The methylation status measured by pyrosequencing was consistent with the methylation array data. Methylation profiling based on beadchip arrays is an effective method for screening aberrantly methylated genes in CRC. In addition, we identified novel methylated genes that are candidate diagnostic or prognostic markers for CRC.
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影响因子：
11.2
作者：
Glöckner SC;Dhir M;Yi JM;McGarvey KE;Van Neste L;Louwagie J;Chan TA;Kleeberger W;de Bruïne AP;Smits KM;Khalid-de Bakker CA;Jonkers DM;Stockbrügger RW;Meijer GA;Oort FA;Iacobuzio-Donahue C;Bierau K;Herman JG;Baylin SB;Van Engeland M;Schuebel KE;Ahuja N
通讯作者：
Ahuja N
整合染色体畸变和基因表达谱以剖析直肠肿瘤发生。
影响因子：
3.8
作者：
Lips, Esther H.;van Eijk, Ronald;de Graaf, Eelco J. R.;Oosting, Jan;de Miranda, Noel F. C. C.;Karsten, Tom;de Velde, Cornelis J. van;Eilers, Paul H. C.;Tollenaar, Rob A. E. M.;van Wezel, Tom;Morreau, Hans
通讯作者：
Morreau, Hans
影响因子：
14.9
作者：
Adorján, P;Distler, J;Olek, A
通讯作者：
Olek, A
影响因子：
4.3
作者：
Liu, Suhu;Ren, Suping;Riker, Adam I.
通讯作者：
Riker, Adam I.
影响因子：
8.8
作者：
Lopez, J.;Percharde, M.;Coley, H. M.;Webb, A.;Crook, T.
通讯作者：
Crook, T.