Mechanism of transformation of neural stem cells by fusion onco-proteins.

Darwin College Sciences Group
Robert Kupp (CRUK Cambridge Institute / Oncology)
The Richard King Room, Darwin College
Thursday, November 15, 2018 - 13:10 to 14:00

Ependymomas are tumors of the central nervous system, arising within the ependymal lining at the ventricle-parenchyma interface. Molecular profiling studies suggests ependymomas in different anatomical compartments are distinct and disparate diseases, with unique cells of origin and genetic drivers. We have recently described a highly recurrent 11q structural variant, producing a fusion translocation between the C11orf95 gene of unknown function and RELA, the principal effector of NF-kB signaling. C11orf95-RELA Fusion proteins, when introduced into neural stem cells, rapidly transform to form ependymoma. Furthermore, recent studies analyzing the genomes and transcriptomes of 500 primary ependymomas have reinforced these findings, showing that C11orf95-RELA fusion proteins are found within ~70% of forebrain (supratentorial) ependymomas and correlated with negative overall survival. However, the molecular events preceding and following Fusion transformation remain largely unknown. In this study we will present our recent efforts integrating transcriptome, proteome, interactome, and genome wide mapping of Fusion proteins (as well as their individual components) to understand the mechanisms by which neural stem cells transform to form ependymomas.

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