Abstract 1361: KDM2A-driven epigenetic reprogramming promotes barrett’s esophagus progression to adenocarcinoma.

Abstract Purpose: Esophageal adenocarcinoma (EAC), a rapidly increasing and highly lethal cancer arising from Barrett’s esophagus (BE), lacks effective preventive strategies. Our study investigates the histone demethylase KDM2A as an early epigenetic driver of BE-to-EAC progression and evaluates whether its inhibition can suppress oncogenic reprogramming and tumorigenesis. Experimental Procedures: We performed high-plex spatial transcriptomics (COSMx, 1K human panel) on patient tissues spanning BE, low- and high-grade dysplasia, and EAC (n = 20), integrating these results with immunohistochemistry, immunofluorescence, and TCGA (n = 186) datasets. Functional studies employed patient-derived organoids (PDOs), xenografts, and CRISPR-based KDM2A perturbation models. Chromatin profiling (CUT Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1361.