Cancer Cell: Amplification of Distant Estrogen Response Elements Deregulates Target Genes Associated with Tamoxifen Resistance in Breast Cancer
Pei-YinHsu1 Hang-KaiHsu1 XunLan6 LiranJuan9 Pearlly S.Yan7 JadwigaLabanowska8 NylaHeerema8 Tzu-HungHsiao4 Yu-ChiaoChiu5 YidongChen34 YunlongLiu9 LangLi9RongLi1I an M.Thompson2 Kenneth P.Nephew10 Zelton D.Sharp 1 Nameer B.Kirma1 Victor X.Jin6 Tim H.-M.Huang1
Summary
A causal role of gene amplification in tumorigenesis is well known, whereas amplification of DNA regulatory elements as an oncogenic driver remains unclear. In this study, we integrated next-generation sequencing approaches to map distant estrogen response elements (DEREs) that remotely control the transcription of target genes through chromatin proximity. Two densely mapped DERE regions located on chromosomes 17q23 and 20q13 were frequently amplified in estrogen receptor-α-positive luminal breast cancer. These aberrantly amplified DEREs deregulated target gene expression potentially linked to cancer development and tamoxifen resistance. Progressive accumulation of DERE copies was observed in normal breast progenitor cells chronically exposed to estrogenic chemicals. These findings may extend to other DNA regulatory elements, the amplification of which can profoundly alter target transcriptome during tumorigenesis.
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