@article {924521,
	title = {PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies.},
	journal = {Nature},
	volume = {514},
	number = {7521},
	year = {2014},
	month = {2014 Oct 9},
	pages = {247-51},
	abstract = {The polycomb repressive complex 2 (PRC2) exerts oncogenic effects in many tumour types. However, loss-of-function mutations in PRC2 components occur in a subset of haematopoietic malignancies, suggesting that this complex plays a dichotomous and poorly understood role in cancer. Here we provide genomic, cellular, and mouse modelling data demonstrating that the polycomb group gene SUZ12 functions as tumour suppressor in PNS tumours, high-grade gliomas and melanomas by cooperating with mutations in NF1. NF1 encodes a Ras GTPase-activating protein (RasGAP) and its loss drives cancer by activating Ras. We show that SUZ12 loss potentiates the effects of NF1 mutations by amplifying Ras-driven transcription through effects on chromatin. Importantly, however, SUZ12 inactivation also triggers an epigenetic switch that sensitizes these cancers to bromodomain inhibitors. Collectively, these studies not only reveal an unexpected connection between the PRC2 complex, NF1 and Ras, but also identify a promising epigenetic-based therapeutic strategy that may be exploited for a variety of cancers.},
	keywords = {Animals, Azepines, Cell Death, Chromatin, Disease Models, Animal, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Glioma, Humans, Melanoma, Mice, Mitogen-Activated Protein Kinase Kinases, Neoplasms, Nerve Sheath Neoplasms, Neurofibromin 1, Nuclear Proteins, Polycomb Repressive Complex 2, ras Proteins, Transcription Factors, Transcription, Genetic, Triazoles, Tumor Suppressor Proteins},
	issn = {1476-4687},
	doi = {10.1038/nature13561},
	author = {De Raedt, Thomas and Beert, Eline and Pasmant, Eric and Luscan, Armelle and Brems, Hilde and Ortonne, Nicolas and Helin, Kristian and Hornick, Jason L and Mautner, Victor and Kehrer-Sawatzki, Hildegard and Clapp, Wade and Bradner, James and Vidaud, Michel and Upadhyaya, Meena and Legius, Eric and Cichowski, Karen}
}
