Abstract A008: Context-specific estrogen receptor alpha chromatin binding and cofactor interactions in ovarian, breast, and uterine cancers

Abstract High grade serous ovarian carcinomas (HGSOC) account for the majority of ovarian cancer diagnoses and unfortunately remain one of the most aggressive and malignant subtypes of epithelial ovarian cancer. While more than half of HGSOC express estrogen receptor alpha (ERα), they do not respond to endocrine chemotherapies with the same success as ERα-positive breast cancers. We propose the hypothesis that ERα association with different cofactors dictates the susceptibility of these cancers to therapies. To support this hypothesis, we analyzed data from cBioportal patient samples which reveals that a strong positive correlation exists between ERα and its cofactors GATA3 and FOXA1 in breast cancer, but not in ovarian and uterine cancers. Furthermore, we analyzed ChIP-seq data from our lab as well as published data to show that ERα genomic localization differs in the three cancer types. Our findings indicate that ERα displays altered chromatin occupancy across cancer types, as well as different co-factor associations. Together, our analyses suggest that that ERα functions in a tissue-specific manner, and that both localization as well as the nature of co-factors might be relevant for driving differential outcomes in ERα-positive tumors of various types. Citation Format: Jenna Grindeland, Motoki Takaku, Archana Dhasarathy. Context-specific estrogen receptor alpha chromatin binding and cofactor interactions in ovarian, breast, and uterine cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl):Abstract nr A008.