CpG站点
DNA甲基化
甲基化
生物
表观遗传学
弥漫性大B细胞淋巴瘤
癌症研究
差异甲基化区
基因
遗传学
分子生物学
基因表达
化疗
作者
Brian L. Pike,Timothy C. Greiner,Xiaoming Wang,Dennis D. Weisenburger,Ya-Hsuan Hsu,Gabriel Renaud,Tyra G. Wolfsberg,Myung-Jin Kim,Daniel J. Weisenberger,Kimberly D. Siegmund,Wei Ye,Susan Groshen,Ruty Mehrian‐Shai,Jan Delabie,Wing C. Chan,Peter W. Laird,Joseph G. Hacia
出处
期刊:Leukemia
[Springer Nature]
日期:2008-02-21
卷期号:22 (5): 1035-1043
被引量:86
摘要
In an initial epigenetic characterization of diffuse large B-cell lymphoma (DLBCL), we evaluated the DNA methylation levels of over 500 CpG islands. Twelve CpG islands (AR, CDKN1C, DLC1, DRD2, GATA4, GDNF, GRIN2B, MTHFR, MYOD1, NEUROD1, ONECUT2 and TFAP2A) showed significant methylation in over 85% of tumors. Interestingly, the methylation levels of a CpG island proximal to FLJ21062 differed between the activated B-cell-like (ABC-DLBCL) and germinal center B-cell-like (GCB-DLBCL) subtypes. In addition, we compared the methylation and expression status of 67 genes proximal (within 500 bp) to the methylation assays. We frequently observed that hypermethylated CpG islands are proximal to genes that are expressed at low or undetectable levels in tumors. However, many of these same genes were also poorly expressed in DLBCL tumors where their cognate CpG islands were hypomethylated. Nevertheless, the proportional reductions in BNIP3, MGMT, RBP1, GATA4, IGSF4, CRABP1 and FLJ21062 expression with increasing methylation suggest that epigenetic processes strongly influence these genes. Lastly, the moderate expression of several genes proximal to hypermethylated CpG tracts suggests that DNA methylation assays are not always accurate predictors of gene silencing. Overall, further investigation of the highlighted CpG islands as potential clinical biomarkers is warranted.
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