Abstract
DNA methylation, a DNA modification by adding methyl group to cytosine, has an important role in the regulation of gene expression. DNA methylation is known to be associated with gene transcription by interfering with DNA-binding proteins, such as transcription factors. DNA methylation is closely related to tumorigenesis, and the methylation state of some genes can be used as a biomarker for tumorigenesis. Aberrant DNA methylation of genomic regions, including CpG islands, CpG shores, and first exons, is related to the altered gene expression pattern characteristics of all human cancers. Subheading 1 surveys recent developments on DNA methylation and gene expressions in cancer. Then we provide analysis of DNA methylation and gene expression in 30 breast cancer cell lines representing different tumor phenotypes. This study conducted an integrated analysis to identify the relationship between DNA methylation in various genomic regions and expression levels of downstream genes, using MethylCapseq data (affinity purification followed by next-generation sequencing of eluted DNA) and Affymetrix gene expression microarray data. The goal of this study was to assess genome-wide methylation profiles associated with different molecular subtypes of human breast cancer (luminal, basal A, and basal B) and to comprehensively investigate the effect of DNA methylation on gene expression in breast cancer phenotypes. This showed that methylation of genomic regions near transcription start sites, CpG island, CpG shore, and first exon was strongly associated with gene repression, and the effects of the regions on gene expression patterns were different for different molecular subtypes of breast cancer. The results further indicated that aberrant methylation of specific genomic regions was significantly associated with different breast cancer subtypes.
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Acknowledgement
This work was supported by the Rural Development Administration(RDA), Next-Generation Information Computing Development Program, the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean Government (MEST) (No. 20120006013) and the Brain Korea 21 Project in 2012.
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Lee, CJ., Evans, J., Kim, K., Chae, H., Kim, S. (2014). Determining the Effect of DNA Methylation on Gene Expression in Cancer Cells. In: Ochs, M. (eds) Gene Function Analysis. Methods in Molecular Biology, vol 1101. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-721-1_9
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DOI: https://doi.org/10.1007/978-1-62703-721-1_9
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