LRRC17 UP in 'SUZ12 overexpression' vs 'wild type'
GPR126 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
HIST2H4A UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
TM6SF1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
PRRX1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
PAPPA-AS1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
BTN3A3 UP in 'SUZ12 overexpression' vs 'wild type'
OAS1 UP in 'SUZ12 overexpression' vs 'wild type'
QRFPR DOWN in 'SUZ12 overexpression' vs 'wild type'
ZSCAN4 UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
CCDC80 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
GCH1 UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
BTN3A2 UP in 'SUZ12 overexpression' vs 'wild type'
PTPRB DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
RP11-665E10.5 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
IFIT2 UP in 'SUZ12 overexpression' vs 'wild type'
IL7R DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
TGFB2 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
(Sample) disease/malignant peripheral nerve sheath tumor
SUZ12 UP in 'SUZ12 overexpression' vs 'wild type'
ACADL DOWN in 'SUZ12 overexpression' vs 'wild type'
S100A2 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
CNN2 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
PNP UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
TMEM244 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
HIST1H4H UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
Analysis of 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
GPM6B DOWN in 'SUZ12 overexpression' vs 'wild type'
PDE1C DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
PRDM1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
TCEAL2 DOWN in 'SUZ12 overexpression' vs 'wild type'
PARP14 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
PARP14 UP in 'SUZ12 overexpression' vs 'wild type'
ANXA3 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
CYP1B1 DOWN in 'SUZ12 overexpression' vs 'wild type'
NPY DOWN in 'SUZ12 overexpression' vs 'wild type'
C7orf69 UP in 'SUZ12 overexpression' vs 'wild type'
NFIB DOWN in 'SUZ12 overexpression' vs 'wild type'
SAMD9L DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
FPR1 UP in 'SUZ12 overexpression' vs 'wild type'
ATP8B1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
IL1B DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
MX2 UP in 'SUZ12 overexpression' vs 'wild type'
IFI44L DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
ANO1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
NRP2 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
Analysis of 'SUZ12 overexpression' vs 'wild type'
RBP7 DOWN in 'SUZ12 overexpression' vs 'wild type'
OAS2 UP in 'SUZ12 overexpression' vs 'wild type'
BAI3 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
ALDH1A1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
KIAA1324L UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
CD274 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
TMEM47 DOWN in 'SUZ12 overexpression' vs 'wild type'
RP11-432M8.8 UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
(Factor value) GENOTYPE/wild type genotype
CHRNA1 UP in 'SUZ12 overexpression' vs 'wild type'
(Factor value) GENOTYPE/SUZ12 overexpression
KLHL24 UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
LPXN DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
FBXL21 DOWN in 'SUZ12 overexpression' vs 'wild type'
ANGPT2 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
C14orf23 UP in 'SUZ12 overexpression' vs 'wild type'
DDX58 UP in 'SUZ12 overexpression' vs 'wild type'
VEPH1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
POSTN DOWN in 'SUZ12 overexpression' vs 'wild type'
HERC6 UP in 'SUZ12 overexpression' vs 'wild type'
SESN3 UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
FGF5 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
OAS1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
IL6 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
XAF1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
LEF1 DOWN in 'SUZ12 overexpression' vs 'wild type'
CCL2 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
SP110 UP in 'SUZ12 overexpression' vs 'wild type'
TNFSF10 UP in 'SUZ12 overexpression' vs 'wild type'
SNORD116-14 UP in 'SUZ12 overexpression' vs 'wild type'
IL1A DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
CCDC84 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
FAP DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
IFIH1 UP in 'SUZ12 overexpression' vs 'wild type'
FGF1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
RSAD2 UP in 'SUZ12 overexpression' vs 'wild type'
The polycomb repressive complex 2 (PRC2) plays an oncogenic role in several cancers. However, loss-of-function mutations in PRC2 components have been detected in a subset of hematopoietic malignancies, suggesting that different epigenetic landscapes are required in different tumor types. In this study we provide genomic, cellular, and mouse modeling data to demonstrate that loss-of-function mutations in the polycomb gene, SUZ12, and NF1 cooperate in peripheral nervous system tumors, glioblastomas, and melanomas. NF1 encodes a Ras GTPase-activating protein and its loss triggers moderate levels of Ras activation. We show that SUZ12-loss enhances the effects of NF1 mutations, in part, by amplifying Ras transcriptional signatures. Moreover, SUZ12-loss triggers an epigenetic switch that confers sensitivity to combined bromodomain and MEK inhibitors in vivo. Collectively these studies demonstrate an unexpected role for polycomb group genes in NF1 mutant tumors and reveal an epigenetic-based therapeutic strategy that may be exploited for a variety of cancers. 9 samples in triplicates, 3x LacZ control, 3x SUZ12 over expression, 3x JQ1 treatment
SAMD9 UP in 'SUZ12 overexpression' vs 'wild type'
PARP9 UP in 'SUZ12 overexpression' vs 'wild type'
ALDH1A1 DOWN in 'SUZ12 overexpression' vs 'wild type'
SULF1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
MPP4 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
RHOJ DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
RBBP6 UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
MAMDC2 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
MPP4 UP in 'SUZ12 overexpression' vs 'wild type'
CCND2 DOWN in 'SUZ12 overexpression' vs 'wild type'
SYNE1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
SCG5 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
NOX4 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
XAF1 UP in 'SUZ12 overexpression' vs 'wild type'
RNVU1-15 UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
ELOVL7 DOWN in 'SUZ12 overexpression' vs 'wild type'
LY6K DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
ATP8A1 UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
C15orf54 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
RFX8 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
FST DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
TRIM51BP UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
LCP1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
ELOVL2 DOWN in 'SUZ12 overexpression' vs 'wild type'
LIFR UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
C15orf54 UP in 'SUZ12 overexpression' vs 'wild type'
TNC DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
HAS2 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
MX1 UP in 'SUZ12 overexpression' vs 'wild type'
SLC14A1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
SAMD9L UP in 'SUZ12 overexpression' vs 'wild type'
IFIT1 UP in 'SUZ12 overexpression' vs 'wild type'
TENM2 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
PTPRD DOWN in 'SUZ12 overexpression' vs 'wild type'
RAB27B UP in 'SUZ12 overexpression' vs 'wild type'
RFPL4AL1 UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
PRKAA2 DOWN in 'SUZ12 overexpression' vs 'wild type'
PDCD1LG2 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
IFIH1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
IFI44L UP in 'SUZ12 overexpression' vs 'wild type'
ELOVL6 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
ANGPT1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
SERPINB7 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
SLC34A2 UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
DHRS2 UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
LPHN3 UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
PSG4 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
BAMBI UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
ADAMTS6 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
KIT DOWN in 'SUZ12 overexpression' vs 'wild type'
RNY3P11 DOWN in 'SUZ12 overexpression' vs 'wild type'
GLT8D2 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
PROM1 DOWN in 'SUZ12 overexpression' vs 'wild type'
RASGRP3 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
SYTL5 UP in 'SUZ12 overexpression' vs 'wild type'
USP41 UP in 'SUZ12 overexpression' vs 'wild type'
NEFM UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
AOX1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
SERPINB2 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
TRERF1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
TMEM47 UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
AK5 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
CDK15 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
CXCL12 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
GATM UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
APOBEC3B DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
IGFBP5 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
RP11-1002K11.1 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
NMU DOWN in 'SUZ12 overexpression' vs 'wild type'
TM4SF18 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
IFI44 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
IFITM1 UP in 'SUZ12 overexpression' vs 'wild type'
FABP4 DOWN in 'SUZ12 overexpression' vs 'wild type'
KCNK2 DOWN in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'
FAM90A27P UP in 'JQ1 100 nanomolar' vs 'DMSO' in 'wild type'