Identification of 20 genes aberrantly methylated in human breast cancers
Identification of 20 genes aberrantly methylated in human breast cancers
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DOI：
10.1002/ijc.21054
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发表时间：
2005-09-01
影响因子：
6.4
通讯作者：
Ushijima, T
中科院分区：
文献类型：
--
作者：
Miyamoto, K;Fukutomi, T;Ushijima, T
CpG岛异常甲基化（CGI）不仅在基因沉默中起作用，而且是一种潜在的癌症生物标志物。为了鉴定人类乳腺癌中更多的CGI异常甲基化，我们使用甲基化敏感性代表性差异分析进行了全基因组异常甲基化搜索。TSPAN-2、AK 5、LOC 284999、HOXD 11、FLJ 25161、XT 3、PCDH 10、PCDHGB 6、SIM 1、LOC 346978、COE 2、TDH等20个基因5'上游区的CGI（FLJ 25033）、L0 C346419、FLJ 33790、GJB 2、AMN、L0 C201164、DLX 4、DCC和FOXA 2在8种乳腺癌细胞系中的至少一种中被甲基化。20个基因中有15个在I期或II期的21个原发性乳腺癌中的一个以上甲基化，特别是LOC 346978、HOXD 11、SIM 1、PCDHGB 6和FLJ 25161的基因在10个以上癌症中甲基化。所有的乳腺癌都有一些异常的甲基化。在CGI在一个或多个细胞系中完全甲基化的13个基因中，FOXA 2和XT 3在正常人乳腺上皮细胞（HMEC）中表达，而在具有完全甲基化的癌细胞系中不表达。其他11个基因在HMEC中几乎不表达或不表达。我们的研究结果表明，乳腺癌细胞积累了这里确定的CGI的异常甲基化。这可能作为早期乳腺癌的标志物，并表明异常甲基化靶向体内转录失活基因。(C)2005 Wiley-Liss，Inc.
Aberrant methylation of CpG islands (CGI) not only plays a role in gene silencing, but is also a potential cancer biomarker. To identify more CGI aberrantly methylated in human breast cancers, we carried out a genome-wide search for aberrant methylation, using methylation-sensitive-representational difference analysis. CGI in 5' upstream regions of 20 genes, TSPAN-2, AK5, LOC284999, HOXD11, FLJ25161, XT3, PCDH10, PCDHGB6, SIM1, LOC346978, COE2, TDH (FLJ25033), LOC346419, FLJ33790, GJB2, AMN, LOC201164, DLX4, DCC and FOXA2, were found to be methylated in at least one of 8 breast cancer cell lines. Fifteen of the 20 genes were methylated in more than one of 21 primary breast cancers in Stages I or II, and especially, those of LOC346978, HOXD11, SIM1, PCDHGB6 and FLJ25161 were methylated in more than 10 cancers. All the breast cancers had some aberrant methylation. Among the 13 genes whose CGI were completely methylated in one or more cell lines, FOXA2 and XT3 were expressed in normal human mammary epithelial cells (HMEC) and were not expressed in cancer cell lines with complete methylation. The other 11 genes examined were barely expressed, or not expressed even in HMEC. Our results showed that breast cancer cells accumulate aberrant methylation of the CGI identified here. This may serve as markers for early-stage breast cancers and suggests that aberrant methylation targets transcriptionally inactive genes in vivo. (C) 2005 Wiley-Liss, Inc.