Transcriptional Reprogramming Differentiates Active from Inactive ESR1 Fusions in Endocrine Therapy-Refractory Metastatic Breast Cancer.

ABSTRACT: Genomic analysis has recently identified multiple ESR1 gene translocations in estrogen receptor alpha-positive (ERα⁺) metastatic breast cancer (MBC) that encode chimeric proteins whereby the ESR1 ligand binding domain (LBD) is replaced by C-terminal sequences from many different gene partners. Here we functionally screened 15 ESR1 fusions and identified 10 that promoted estradiol-independent cell growth, motility, invasion, epithelial-to-mesenchymal transition, and resistance to fulvestrant. RNA sequencing identified a gene expression pattern specific to functionally active ESR1 gene fusions that was subsequently reduced to a diagnostic 24-gene signature. This signature was further examined in 20 ERα⁺ patient-derived xenografts and in 55 ERα⁺ MBC sam

SUBMITTER: Gou X 

PROVIDER: S-EPMC9234971 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature