Differential methylation hybridization profiling identifies involvement of STAT1-mediated pathways in breast cancer

  • Authors: Ju Hee Kim, Han-Sung Kang, Tae Woo Kim, Sun Jung Kim
  • View Affiliations

  • Published online on: Tuesday, June 14, 2011
  • Pages: 955-963
  • DOI: 10.3892/ijo.2011.1075

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.
Journal Cover

October 2011
Volume 39 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2012 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

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APA
Kim, J., Kim, J., Kang, H., Kang, H., Kim, T., Kim, T., Kim, S., & Kim, S. (2011). Differential methylation hybridization profiling identifies involvement of STAT1-mediated pathways in breast cancer. International Journal of Oncology, 39(4), 955-963.
MLA
Kim, Kim, Kang, Kang, Kim, Kim, Kim, and Sun Kim. "Differential methylation hybridization profiling identifies involvement of STAT1-mediated pathways in breast cancer." International Journal of Oncology International Journal of Oncology 39.4 (2011): 955-963.
Chicago
Kim, Kim, Kang, Kang, Kim, Kim, Kim, and Sun Kim. "Differential methylation hybridization profiling identifies involvement of STAT1-mediated pathways in breast cancer." International Journal of Oncology International Journal of Oncology 39 no. 4 (2011): 955-963.