CUT&RUN profiling of EZH2, H3K27me3, and H3K4me3 enrichment in FACS-sorted CD70⁻ and CD70⁺ tumor cells from untreated ex vivo ccRCC and HGSOC patient-derived xenografts.

CD70 expression in solid tumors is heterogeneous. We demonstrate that cells appearing CD70-negative retain ultra-low levels of CD70 expression. These cells that appear negative by conventional detection methods. Bulk ATAC-seq analysis of FACS-sorted CD70⁻ and CD70⁺ tumor populations revealed differential chromatin accessibility, indicating epigenetic regulation of CD70 expression in both ccRCC and HGSOC models. CUT&RUN profiling of EZH2, H3K27me3, and H3K4me3 in FACS-sorted CD70⁻ and CD70⁺ tumor cells derived from ccRCC and HGSOC PDXs revealed enrichment of differential repressive and activating histone modifications.