Identification and validation of an ESR1 Y537S mutant-specific enhancer and its downstream target IGFBP3 [ATAC-seq]

However, resistance to endocrine therapy occurs in a significant proportion of patients, and hotspot missense point mutations of the ESR1 gene that codes ER-alpha is one of the major underlying mechanisms for such resistance.

While recent research has provided novel insights into the role and activities of mutant ER, effective therapeutics that can overcome this mutant ER-mediated endocrine resistance remain elusive. Employing circulating tumor cell line carrying the ESR1 Y537S mutation derived from a metastatic breast cancer patient, along with genetically engineered breast cancer cell lines harboring the same mutation, our analysis identified a novel enhancer region that is specifically bound by Y537S mutant ER.