Landscape of genome-wide age-related DNA methylation in breast tissue.
Song MA, Brasky TM, Weng DY, McElroy JP, Marian C, Higgins MJ, Ambrosone C, Spear SL, Llanos AA, Kallakury BVS, Freudenheim JL, Shields PG
Oncotarget 8 114648-114662 12/29/2017
Despite known age-related DNA methylation (aDNAm) changes in breast tumors, little is known about aDNAm in normal breast tissues. Breast tissues from a cross-sectional study of 121 cancer-free women, were assayed for genome-wide DNA methylation. mRNA expression was assayed by microarray technology. Analysis of covariance was used to identify aDNAm's. Altered methylation was correlated with expression of the corresponding gene and with DNA methyltransferase protein DNMT3A, assayed by immunohistochemistry. Publically-available TCGA-BRCA data were used for replication. 1,214 aDNAm's were identified; 97% with increased methylation, and all on autosomes. Sites with increased methylation were predominantly in CpG lslands and non-enhancers. aDNAm's with decreased methylation were generally located in intergenic regions, non-CpG Islands, and enhancers. Of the aDNAm's identified, 650 are known to be involved in cancer, includingFull Text