DNA hypermethylation accompanied by transcriptional repression in follicular lymphoma.
DNA hypermethylation accompanied by transcriptional repression in follicular lymphoma.
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DOI：
10.1002/gcc.20687
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发表时间：
2009-09
影响因子：
3.7
通讯作者：
Caldwell, Charles W.
中科院分区：
文献类型：
--
作者：
Bennett, Lynda B.;Schnabel, Jennifer L.;Kelchen, Jean M.;Taylor, Kristen H.;Guo, Juyuan;Arthur, Gerald L.;Papageorgio, Christos N.;Shi, Huidong;Caldwell, Charles W.
采用高通量基因芯片技术研究滤泡性淋巴瘤（FL）中DNA甲基化及其伴随的转录水平变化。使用甲基化CpG岛扩增芯片（MCAM）研究滤泡性淋巴瘤（FL）中的CpG岛（CGI）DNA甲基化，我们发现了细胞系和原发性肿瘤中广泛存在的同源异型盒基因和先前确定的多梳抑制复合物2（PRC 2）靶基因的高甲基化，但在良性滤泡性增生（BFH）中没有发现。在RL细胞系中独立验证了HOXA 11、HOXD 10、HOXB 7、HOXC 12、PAX 6、LHX 9、SFMBT 2、EN 2和PAX 7的DNA甲基化，在原发性肿瘤中独立验证了HOXA 11、HOXD 10、PAX 6和EN 2的DNA甲基化。联合亚硫酸氢盐限制性分析（COBRA）还确定了先前鉴定的PRC 2靶标DCC、DES、GAD 2、AQP 5、GPR 61、GRIA 4、GJD 2和AMPH在FL中的DNA甲基化，但在BFH中没有。基因表达分析显示，RL中有411个基因被高甲基化和转录抑制，其中74%被去甲基化剂5-氮杂-2 '-脱氧胞苷（5-azaD）加或减组蛋白去乙酰化酶抑制剂曲古抑菌素A（TSA）重新激活。我们的研究结果表明，广泛的高甲基化的polycomb靶基因的启动子FL的一个特点，某些SUZ 12靶基因的表达损失可能是功能相关的淋巴瘤。
High-throughput microarray technologies were used to study DNA methylation accompanied by transcriptional changes in follicular lymphoma (FL). Using Methylated CpG Island Amplification with Microarrays (MCAM) to study CpG Island (CGI) DNA methylation in follicular lymphoma (FL) we discovered widespread hypermethylation of homeobox genes and previously identified targets of polycomb repressive complex 2 (PRC2) in cell lines and primary tumors, but not in benign follicular hyperplasia (BFH). DNA methylation for HOXA11, HOXD10, HOXB7, HOXC12, PAX6, LHX9, SFMBT2, EN2 and PAX7 was independently validated in the RL cell line and HOXA11, HOXD10, PAX6 and EN2 in primary tumors. Combined Bisulfite Restriction Analysis (COBRA) also established DNA methylation for the previously identified PRC2 targets DCC, DES, GAD2, AQP5, GPR61, GRIA4, GJD2 and AMPH in FL but not in BFH. Gene expression analyses revealed 411 genes that were hypermethylated and transcriptionally repressed in RL, 74% of which were re-activated by the demethylating agent 5-aza-2′-deoxycytidine (5-azaD) plus or minus the histone deacetylase inhibitor trichostatin A (TSA). Forty genes were also down-regulated in primary FL. Our results suggest that extensive hypermethylation in promoters of polycomb target genes is a characteristic of FL and that loss of expression of certain SUZ12 target genes could be functionally relevant for lymphomagenesis.
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DOI：
10.1007/978-1-59745-522-0_6
发表时间：
2009
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Rauch, Tibor A.;Pfeifer, Gerd P.
通讯作者：
Pfeifer, Gerd P.
影响因子：
8
作者：
Huang, M;Kamasani, U;Prendergast, GC
通讯作者：
Prendergast, GC
影响因子：
64.5
作者：
Czermin, B;Melfi, R;Pirrotta, V
通讯作者：
Pirrotta, V
影响因子：
16
作者：
Cao, R;Zhang, Y
通讯作者：
Zhang, Y
影响因子：
16
作者：
Feng, XH;Liang, YY;Lin, X
通讯作者：
Lin, X