DREAM target reactivation by core transcriptional regulators supports neuroblastoma growth

Bieke Decaesteker; Katleen De Preter; Frank Speleman

doi:10.1080/23723556.2019.1565470

DREAM target reactivation by core transcriptional regulators supports neuroblastoma growth

Mol Cell Oncol. 2019 Feb 3;6(2):1565470. doi: 10.1080/23723556.2019.1565470. eCollection 2019.

Authors

Bieke Decaesteker^{1

2}, Katleen De Preter^{1

2}, Frank Speleman^{1

2}

Affiliations

¹ Center for Medical Genetics, Ghent University, Ghent, Belgium.
² Ghent University, Cancer Research Institute Ghent (CRIG), Ghent 9000, Belgium.

Abstract

Chromosome 17q gains are a common alteration in high-risk neuroblastomas with unknown functional significance. We identified a 17q super-enhancer regulated T-box Transcription Factor 2 (TBX2) as constituent of a core regulatory circuitry driving proliferation through enhancing V-myc myelocytomatosis viral-related oncogene, neuroblastoma derived (avian) (MYCN)/Forkhead box protein M1(FOXM1) reactivation of dimerization partner, RB-like, E2F and multi-vulval class B (DREAM) targets, which can be affected synergistically by combined cyclin-dependent kinase 7 and Bromo-domain inhibition.

Keywords: FOXM1; MYCN; TBX2; core regulatory circuitry; neuroblastoma.

Grants and funding

This work was supported by the Belgian Foundation Against Cancer under Grant project 2015-146; Ghent University under Grant BOF10/GOA/019 and BOF16/GOA/23; the Belgian Program of Interuniversity Poles of Attraction under Grant IUAP Phase VII – P7/03; the Fund for Scientific Research Flanders under Grant Research projects G053012N, G050712N, G051516N, G021415N; the “Kom op tegen Kanker“ (Stand up to Cancer) the Flemish Cancer Society; the European Union H2020 under Grant OPTIMIZE-NB GOD9415N and TRANSCAN-ON THE TRAC GOD8815N; ‘Kinderkankerfonds’; Olivia Fund; and Villa Joep