Abstract 999: Epigenetic loss of heterogeneity from low to high grade localized prostate tumors

Abstract Identifying precise molecular subtypes attributable to specific stages of localized prostate cancer has proven difficult due to high levels of heterogeneity. Bulk assays represent a population-average, which mask the heterogeneity that exists at the single-cell level. In this work, we sequenced the accessible chromatin regions of 14,424 single-cells from 18 flash-frozen prostate tumors. We observe shared chromatin features among low-grade prostate cancer cells are lost in high-grade tumors. Despite this loss, high-grade tumors exhibit an enrichment for FOXA1, HOXB13 and CDX2 transcription factor binding sites, indicating a shared trans-regulatory program. We identify two unique genes encoding neuronal adhesion molecules that are highly accessible in high-grade prostate tumors. We show NRXN1 and NLGN1 expression in epithelial, endothelial, immune and neuronal cells in prostate cancer using cyclic immunofluorescence. Our results provide a deeper understanding of the active gene regulatory networks in primary prostate tumors, critical for molecular stratification of the disease. Citation Format: Ece Sebnem Eksi, Zeynep Sayar, Alex Chitsazan, George T. Thomas, Andrew Adey, Paul T. Spellman, Ryan Kopp. Epigenetic loss of heterogeneity from low to high grade localized prostate tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 999.