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Detailed DNA methylation profiles of the E-cadherin promoter in the NCI-60 cancer cells
William C. Reinhold, Mark A. Reimers, Alika K. Maunakea, Sohyoung Kim, Samir Lababidi, Uwe Scherf,
Uma T. Shankavaram, Micah S. Ziegler, Claudia Stewart, Hosein Kouros-Mehr, Hengmi Cui, Douglas Dolginow, Dominic A. Scudiero,
Yves G. Pommier, David J. Munroe, Andrew P. Feinberg and John N. Weinstein
Molecular Cancer Therapeutics 6, 391-403, February 1, 2007. Published Online First February 1, 2007
Abstract:
E-cadherin (E-cad) is a transmembrane adhesion glycoprotein, the expression of which is often reduced in
invasive or metastatic tumors. To assess E-cad's distribution among different types of cancer cells, we used bisulfite-sequencing
for detailed, base-by-base measurement of CpG methylation in E-cad's promoter region in the NCI-60 cell lines. The mean
methylation levels of the cell lines were distributed bimodally, with values pushed toward either the high or low end of the
methylation scale. The 38 epithelial cell lines showed substantially lower (28%) mean methylation levels compared with the
nonepithelial cell lines (58%). The CpG site at -143 with respect to the transcriptional start was commonly methylated at
intermediate levels, even in cell lines with low overall DNA methylation. We also profiled the NCI-60 cell lines using
Affymetrix U133 microarrays and found E-cad expression to be correlated with E-cad methylation at highly statistically
significant levels. Above a threshold of approximately 20% to 30% mean methylation, the expression of E-cad was effectively
silenced. Overall, this study provides a type of detailed analysis of methylation that can also be applied to other
cancer-related genes. As has been shown in recent years, DNA methylation status can serve as a biomarker for use in choosing
therapy. [Mol Cancer Ther 2007;6(2):391-403].
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