Identification of 20 genes aberrantly methylated in human breast cancers
Article first published online: 7 APR 2005
Copyright © 2005 Wiley-Liss, Inc.
International Journal of Cancer
Volume 116, Issue 3, pages 407–414, 1 September 2005
How to Cite
Miyamoto, K., Fukutomi, T., Akashi-Tanaka, S., Hasegawa, T., Asahara, T., Sugimura, T. and Ushijima, T. (2005), Identification of 20 genes aberrantly methylated in human breast cancers. Int. J. Cancer, 116: 407–414. doi: 10.1002/ijc.21054
- Issue published online: 10 JUN 2005
- Article first published online: 7 APR 2005
- Manuscript Accepted: 26 JAN 2005
- Manuscript Received: 14 OCT 2004
- The third-term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare, Japan
- Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan
- breast cancer;
- CpG island;
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. © 2005 Wiley-Liss, Inc.