Project

The chromatin modifier BRD3 as a key novel player in DNA repair and vulnerable therapeutic target in neuroblastoma

Code
31506718
Duration
01 January 2018 → 31 December 2018
Funding
Research Foundation - Flanders (FWO)
Research disciplines
No data available
Keywords
dna repair
 
Project description

Embryonal tumors, like neuroblastoma, have often been considered as disorders in early

development through perturbation of normal differentiation of immature progenitor cells.

Interestingly, during the past decade our view on the genetic causes of cancers has dramatically

expanded, most notably with the finding that more than 20% of all genes mutated in cancer affects

epigenetically controlled processes. Epigenetic regulation of cell identity genes, is crucial during

normal development and perturbation of this tightly controlled process also contributes to cancer

formation. In this respect, the ‘romodomain and extraterminal’(BET) protein family member BRD4

has been shown to play a key role in rewiring of transcriptional networks in malignant

transformation in many cancer types through its activity at super-enhancer sites aberrantly driving

oncogene activation. In contrast, the role of other members of the BET protein family in cancer

development is only poorly characterized. Our research team identified BRD3 as a novel crucial

component of the MYCN driven transcriptome in neuroblastoma. Preliminary dissection of the

putative interaction partners for BRD3 revealed unexpectedly its connectivity to the DNA damage

response pathway and replicative stress resistance, which provides a powerful lead for novel

therapeutic avenues for treatment of neuroblastoma patients.