Abstract B011: FOXA1 as a pioneer factor in ERα-DNA interactions and its therapeutic potential in ER+ breast cancer: Insights from ChIP-seq and GWAS in Hispanic populations

Abstract

Abstract Forkhead box A1 (FOXA1) acts as a pioneer factor for Estrogen Receptor alpha (ERα), playing a crucial role in determining where ERα binds to DNA and regulates gene expression in breast cancer cells. A pioneer factor is a class of transcription factors (TF) that is responsible for opening the chromatin to allow other TFs to attach and activate transcription of that gene. FOXA1 acts as a facilitator for ERα-DNA interactions. It binds to specific DNA regions, opening the chromatin for ERα to bind. It “pre-marks” these sites in the genome even in the absence of estrogen. In fact, FOXA1 is frequently overexpressed in ER+ breast cancers, suggesting it has a crucial role in driving tumor growth. As such, FOXA1 is an attractive therapeutic target that already serves as a great biomarker for many types of breast cancers. Inhibiting FOXA1 can potentially block ER activity and inhibit growth of ER+ breast cancer, especially in those resistant to anti-estrogen therapies, such as tamoxifen. In this project, we identified sites that FOXA1 opens and correlated them with SNP mutations commonly found in the Hispanic population. The presence of these SNPs portends a worse outcome in Hispanic patients. To assess which open chromatin regions are crucial for breast cancer pathogenesis, a ChIP-seq analysis was done on vehicle-treated and estrogen-treated samples to determine FOXA1 binding sites. After identifying gained, lost, and differentially expressed peaks set, these were compared to genome-wide association studies (GWAS) of Hispanic patients to develop an understanding of how much overlap is common between sites of mutations and open sections of chromatin due to FOXA1. Through our analysis, we uncovered a subset of FOXA1 binding sites that overlap with sites of inherited mutation in Hispanic patients. This informs on the subset of genes that are linked to breast cancer and potential therapeutic targets. Citation Format: Hemakshat Sharma, Alyssa Maria Arreola, Frances L. Heredia, Hector L. Franco, Julie Dutil. FOXA1 as a pioneer factor in ERα-DNA interactions and its therapeutic potential in ER+ breast cancer: Insights from ChIP-seq and GWAS in Hispanic populations [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B011.