SUZ12 and NF1 loss cooperate to enhance Ras transcriptional output and sensitize cancers to epigenetic therapies

ABSTRACT: 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 confe

ORGANISM(S): Homo sapiens

SUBMITTER: Thomas De Raedt 

PROVIDER: E-GEOD-52777 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress