PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies [ChIP-seq]

ABSTRACT: The polycomb repressive complex 2 (PRC2) exerts oncogenic effects in many tumour types1. 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 cancer2,3. Here we provide genomic, cellular, and mouse mod- elling data demonstrating that the polycomb group gene SUZ12 func- tions 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 Ras4. 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 trigg

ORGANISM(S): Homo sapiens

SUBMITTER: Thomas De Raedt 

PROVIDER: E-GEOD-62499 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress