title: Differential methylation relative to breast cancer subtype and matched normal tissue reveals distinct patterns.
abstract: Due to the heterogeneous nature of breast cancer and the widespread use of single-gene studies, there is limited knowledge of multi-gene, locus-specific DNA methylation patterns in relation to molecular subtype and clinical features. We, therefore, quantified DNA methylation of 70 candidate gene loci in 140 breast tumors and matched normal tissues and determined associations with gene expression and tumor subtype. Using Sequenom's EpiTYPER platform, approximately 1,200 CpGs were interrogated and revealed six DNA methylation patterns in breast tumors relative to matched normal tissue. Differential methylation of several gene loci was observed within all molecular subtypes, while other patterns were subtype-dependent. Methylation of numerous gene loci was inversely correlated with gene expression, and in some cases, this correlation was only observed within specific breast tumor subtypes. Our findings were validated on a larger set of tumors and matched adjacent normal tissue from The Cancer Genome Atlas dataset, which utilized methylation data derived from both Illumina Infinium 27 and 450 k arrays. These findings highlight the need to control for subtype when interpreting DNA methylation results, and the importance of interrogating multiple CpGs across varied gene regions.
authors.affiliation: School of Nursing, The University of North Carolina at Chapel Hill, Office 5102, Carrington Hall, CB #7460, Chapel Hill, NC, 27599-7460, USA.
authors.forename: Sabrina A
authors.initials: SA
authors.lastname: Bardowell
authors.forename: Joel
authors.initials: J
authors.lastname: Parker
authors.forename: Cheng
authors.initials: C
authors.lastname: Fan
authors.forename: Jamie
authors.initials: J
authors.lastname: Crandell
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.forename: Theresa
authors.initials: T
authors.lastname: Swift-Scanlan
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D012016:Reference Values; D015203:Reproducibility of Results