Integrated analysis of genome-wide DNA methylation and gene expression profiles in molecular subtypes of breast cancer

Je Keun Rhee, Kwangsoo Kim, Heejoon Chae, Jared Evans, Pearlly Yan, Byoung Tak Zhang, Joe Gray, Paul Spellman, Tim H.M. Huang, Kenneth P. Nephew, Sun Kim

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Aberrant DNA methylation of CpG islands, CpG island shores and first exons is known to play a key role in the altered gene expression patterns in all human cancers. To date, a systematic study on the effect of DNA methylation on gene expression using high resolution data has not been reported. In this study, we conducted an integrated analysis of MethylCap-sequencing data and Affymetrix gene expression microarray data for 30 breast cancer cell lines representing different breast tumor phenotypes. As well-developed methods for the integrated analysis do not currently exist, we created a series of four different analysis methods. On the computational side, our goal is to develop methylome data analysis protocols for the integrated analysis of DNA methylation and gene expression data on the genome scale. On the cancer biology side, we present comprehensive genome-wide methylome analysis results for differentially methylated regions and their potential effect on gene expression in 30 breast cancer cell lines representing three molecular phenotypes, luminal, basal A and basal B. Our integrated analysis demonstrates that methylation status of different genomic regions may play a key role in establishing transcriptional patterns in molecular subtypes of human breast cancer.

Original languageEnglish (US)
Pages (from-to)8464-8474
Number of pages11
JournalNucleic acids research
Volume41
Issue number18
DOIs
StatePublished - Oct 1 2013

ASJC Scopus subject areas

  • Genetics

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    Rhee, J. K., Kim, K., Chae, H., Evans, J., Yan, P., Zhang, B. T., Gray, J., Spellman, P., Huang, T. H. M., Nephew, K. P., & Kim, S. (2013). Integrated analysis of genome-wide DNA methylation and gene expression profiles in molecular subtypes of breast cancer. Nucleic acids research, 41(18), 8464-8474. https://doi.org/10.1093/nar/gkt643