GSE266407 ESR1 fusions invoke breast cancer subtype-dependent enrichment of ligand independent oncogenic signatures and phenotypes [ChIP-seq]

Contributors : Megan E Yates ; Zheqi Li ; Yiting Li ; Hannah Guzolik ; Xiaosong Wang ; Tiantong Liu ; Jagmohan Hooda ; Jennifer M Atkinson ; Adrian V Lee ; Steffi OesterreichSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensBreast cancer is a leading cause of female mortality and despite advancements in personalized therapeutics, metastatic disease largely remains incurable due to drug resistance. The estrogen receptor (ER, ESR1) is expressed in two-thirds of all breast cancer, and under endocrine stress, somatic ESR1 mutations arise in ~30% of cases that result in endocrine resistance. We and others reported ESR1 fusions as a mechanism of ER mediated endocrine resistance. ER fusions, which retain the AF1 and DNA binding domains, harbor ESR1 exons 1-6 fused to an in-frame gene partner resulting in loss of the ER ligand binding domain (LBD). We demonstrate that in a no-special type (NST) and an invasive lobular carcinoma (ILC) cell line, ER fusions exhibit robust hyperactivation of canonical ER signaling pathways independent of estradiol or anti-endocrine therapies. We employ cell line models stably overexpressing ER fusions with concurrent endogenous ER knockdown to minimize endogenous ER influence. Cell lines exhibited shared transcriptomic enrichment in pathways known to be drivers of metastatic disease, notably MYC signaling. Cells expressing the 3 ’ fusion partners SOX9 and YAP1 consistently demonstrated enhanced...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research