title: Differential methylation hybridization profiling identifies involvement of STAT1-mediated pathways in breast cancer.
abstract: Many cancer-related genes are regulated by an epigenetic mechanism through modification of the methylation status of CpG sites at the promoter. This study was carried out at a genome-wide scale to mine genes in which the methylation of CpG sites is altered in breast cancer tissues. Differential methylation hybridization analysis was conducted using a chromosomal DNA mixture of ten normal and cancer tissue sets. A CpG microarray harboring 237,220 CpG sites of the whole genome was interrogated and the resulting methylation level differences, as well as the RNA expression differences, between the normal and cancer sets for selected genes were verified in breast cell lines by methylation-specific PCR and real-time PCR analyses. As a result, we identified and verified novel genes that were hypermethylated in breast cancer, such as NRN1, CA5B and RPIA. Pathway analysis of the genes with altered methylation patterns identified the involvement of a differentiation-related network of genes whose activity may be heavily regulated by STAT1 in breast tumorigenesis. Our results suggest that epigenetic dysregulation of cellular processes relevant to STAT1-dependent cellular differentiation may be intimately involved in breast carcinogenesis. These findings lend credence to the possibility of using tumor-specific alterations in methylation patterns as biomarkers in estimating prognosis and assessing treatment options for breast cancer.
authors.affiliation: Department of Life Science, Dongguk University-Seoul, Seoul 100-715, Republic of Korea.
authors.forename: Ju Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Han-Sung
authors.initials: HS
authors.lastname: Kang
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Kim
authors.forename: Sun Jung
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D006824:Hybridization, Genetic; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011401:Promoter Regions, Genetic; D050794:STAT1 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human