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Identification of 20 genes aberrantly methylated in human breast cancers
Author(s) -
Miyamoto Kazuaki,
Fukutomi Takashi,
AkashiTanaka Sadako,
Hasegawa Tadashi,
Asahara Toshimasa,
Sugimura Takashi,
Ushijima Toshikazu
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21054
Subject(s) - methylation , biology , breast cancer , dna methylation , gene silencing , cancer research , cpg site , gene , cancer , microbiology and biotechnology , genetics , gene expression
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.