Extended Data Figure 4: Consequences of SUZ12 loss on drug sensitivity and H3K27me3 levels.
From: PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies
a, Graph depicting log2 fold change in MPNST cell number (90-8TL) after 3 days in response to drugs and siRNA sequences indicated. PD-0325901 also cooperates with genetic BRD4 ablation to kill cells. b, Relative expression of BRD4 as determined by real-time PCR after exposure to BRD4-specific siRNAs (90-8TL). c, SUZ12 ablation using shSUZ12 S1 conferred increased sensitivity to combined PD-901/JQ1 in NF1-deficient but not NF1 WT colon cancer and GBM cell lines. Log2 fold change in cell number was determined. RKO, DLD1 and Caco cell lines were treated with 1 μM JQ1 and 1 μM PD901 each time alone or in combination. The Lovo cell line was treated with 500 nM JQ1 and 250 M PD901; SW480 was treated with 250 nM PD901 and 1 μM JQ1; LN229 and A172 cell lines were treated with 500 nM JQ1 and 1 μM PD901. d, Immunohistochemistry comparing H3K27me3 expression in an additional human MPNST that was WT for SUZ12 and other PRC2 genes, and one that was null for SUZ12. Arrow depicts positive staining of blood vessel. Staining of additional tumours is shown in Extended Data Table 1. Error bars, s.d. (n = 3, biological replicates).
