Extended Data Fig. 1. Further characterization of LSD1/CoREST in breast cancer and long-term estrogen deprivation (LTED) model.
a, Kaplan–Meier survival curves segregated by ERα expression and TP53 mutation status (METABRIC dataset of 1,423 samples). Overall survival of patients with ER-/TP53 mutations is significantly diminished. P value was calculated using a log-rank (Mantel–Cox) test. b, CD24 and CD44 expression after 12 months (M) in LTED. c, FACS of T47D-LTED biological replicate (FM, full media). d-e, CD24 and CD44 expression in FM, TamR, FulR, and LTED T47D (d) and MCF7 (e). f, Growth curves of 2 × 105 FM and LTED T47D (3–9M) cultured with DMSO (vehicle) or 1µM tamoxifen or fulvestrant for 5 days, n=3 biological independent replicates, data are presented as mean values + SEM, p-value < 0.001 (two-way ANOVA). g, Heatmap of 3,206 significantly downregulated genes (FC > 2, q-value < 0.05) during acquisition of resistance in T47D. Major transcriptomic changes occurred after 6M in LTED. h, GSEA of 4M and 6M T47D-LTED cells. Basal breast cancer, EMT transition, and ductal invasive signatures were upregulated while response to estrogen and luminal breast cancer signatures were downregulated after 6 months in LTED conditions. NES, normalized enrichment score. i, Single-cell SNV (single nucleotide variant) analysis from 6 × 103 FM and 6M T47D-LTED. No FM cells harboured BRAF or KRAS mutations while ~60% of 6M cells acquired mutations in both genes. j, RNA-seq signal at ESR1 and PGR in FM and 9M T47D-LTED.