title: Integrated analysis of genome-wide DNA methylation and gene expression profiles in molecular subtypes of breast cancer.
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.
authors.affiliation: Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-742, Korea, Bioinformatics Institute, Seoul National University, Seoul 151-744, Korea, School of Informatics and Computing, Indiana University, Bloomington, IN 47408, USA, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN 55905, USA, The Ohio State University Comprehensive Cancer Center Nucleic Acid Shared Resource-Illumina Core, Columbus, OH 43210, USA, School of Computer Science and Engineering, Seoul National University, Seoul 151-742, Korea, OHSU Knight Cancer Institute, Portland, OR 97239, USA, Department of Molecular Medicine/Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA, Medical Sciences, Indiana University School of Medicine, Bloomington, IN 47405, USA and Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Je-Keun
authors.initials: JK
authors.lastname: Rhee
authors.forename: Kwangsoo
authors.initials: K
authors.lastname: Kim
authors.forename: Heejoon
authors.initials: H
authors.lastname: Chae
authors.forename: Jared
authors.initials: J
authors.lastname: Evans
authors.forename: Pearlly
authors.initials: P
authors.lastname: Yan
authors.forename: Byoung-Tak
authors.initials: BT
authors.lastname: Zhang
authors.forename: Joe
authors.initials: J
authors.lastname: Gray
authors.forename: Paul
authors.initials: P
authors.lastname: Spellman
authors.forename: Tim H-M
authors.initials: TH
authors.lastname: Huang
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Nephew
authors.forename: Sun
authors.initials: S
authors.lastname: Kim
mesh_terms: D001665:Binding Sites; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics / Q000379:methods; D006801:Humans; D010641:Phenotype; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors