Fig. 7: ERG oncogenicity depends on KMT2A/MLL1 and DOT1L but not MENIN.
From: ERG-driven prostate cancer initiation is cell-context dependent and requires KMT2A and DOT1L
a, Violin plots comparing inferred expression of a panel of histone-modifying enzymes across all epithelial clusters from scATAC-seq. b, Box plot showing expression of indicated genes in human PCa from two public datasets, separated by ERG-fusion status. n = 181 (ERG−), 152 (ERG+) for TCGA; n = 108 (ERG−), 100 (ERG+) for SU2C. The center line represents the median, the box limits represent the upper and lower quartiles, and the minimum and maximum whiskers represent the 10th and 90th percentiles, respectively. c, DepMap dependency scores of human prostate cell lines. A negative CRISPR score indicates dependency (n = 8 for ETS−, n = 2 for ETS+ lines). ETS TF positive cell lines, VCaP (ERG+) and LNCaP (ETV1+), are highlighted. The center line represents the median, the box limits represent the upper and lower quartiles, and the minimum and maximum whiskers represent the minimum and maximum, respectively. d, Luminal output quantified by flow cytometry (left to right: n = 7, 2, 2, 2, 3, 3 independent assays). EP reporter organoids were treated with indicated guide RNAs and analyzed 2 weeks later. e, Schematic showing orthotopic transplantation assay using engineered tumor-derived organoids. Whole prostates of EPC mice (3–9 months) were pooled, edited and shortly expanded in organoid culture before transplantation into dorsal lobes of host mice (2 months old). Prostates were collected 5~7 weeks after grafting. f–h, Histology and tumor area quantification of orthografts with Kmt2a (f), Dot1l (g) and Men1 (h) perturbation. Left to right: n = 16, 8, 6 grafts (f); n = 14, 12, 6, 14 grafts (g); n = 6, 2, 6, 6 grafts (g). Tumor areas were quantified as highlighted, based on ERG (f), ERG and loss of H3K79me2 (g), ERG and loss of Menin (h). H3K79me2 immunohistochemistry is shown in Extended Data Fig. 10c. Scale bars, 250 µm. Data represent mean ± s.d.; two-tailed unpaired t-test (b,c); one-way ANOVA with Dunnett posttest (d); one-way ANOVA with Tukey posttest (f–h). Neg, negative; Pos, positive.
