GSE244844 ERa profiling in human breast tumors reveals high inter-patient heterogeneity with enrichment of risk SNPs and enhancer activity at most-conserved regions [Hi-C]

Contributors : Stacey E Joosten ; Sebastian Gregoricchio ; Suzan Stelloo ; Elif Yap ıcı ; Chia-Chi F Huang ; Maria Donaldson Collier ; Tunc Morova ; Berkay Altintas ; Yongsoo Kim ; Sander Canisius ; Gozde Korkmaz ; Nathan Lack ; Michiel Vermeulen ; Sabine C Linn ; Wilbert ZwartSeries Type : OtherOrganism : Homo sapiensEstrogen Receptor alpha (ERa) is the main driver of luminal breast cancer development and progression, and represents the main drug target in patient care. ERa chromatin binding has been extensively studied in breast cancer cell lines and a number of human tumors, often focused on differential binding patterns between groups or conditions. However, little is known about the inter-tumor heterogeneity of ERa chromatin action. Here, we use a large set of ERa ChIP-seq data from 70 ERa+ breast cancers (40 women and 30 men) to explore general inter-patient heterogeneity in ERa DNA binding in breast cancers. We found a total universe of 84,565 and 101,653 ERa sites in females and males respectively, with merely 1.2% and 5% of sites shared in at least half of the tumors analyzed, reflecting a high level of inter-patient heterogeneity. This heterogeneity was found to be most variable at putative enhancers as opposed to promoter regions, potentially reflecting a level of functional redundancy in enhancer action. Interestingly, commonly shared ERa sites showed the highest estrogen-driven enhancer activity, as determined using a massive parallel reporter ass...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Other Homo sapiens Source Type: research