Super enhancers define regulatory subtypes and cell identity in neuroblastoma.
Nat Cancer
; 2(1): 114-128, 2021 01.
Article
en En
| MEDLINE
| ID: mdl-35121888
ABSTRACT
Half of the children diagnosed with neuroblastoma (NB) have high-risk disease, disproportionately contributing to overall childhood cancer-related deaths. In addition to recurrent gene mutations, there is increasing evidence supporting the role of epigenetic deregulation in disease pathogenesis. Yet, comprehensive cis-regulatory network descriptions from NB are lacking. Here, using genome-wide H3K27ac profiles across 60 NBs, covering the different clinical and molecular subtypes, we identified four major super-enhancer-driven epigenetic subtypes and their underlying master regulatory networks. Three of these subtypes recapitulated known clinical groups; namely, MYCN-amplified, MYCN non-amplified high-risk and MYCN non-amplified low-risk NBs. The fourth subtype, exhibiting mesenchymal characteristics, shared cellular identity with multipotent Schwann cell precursors, was induced by RAS activation and was enriched in relapsed disease. Notably, CCND1, an essential gene in NB, was regulated by both mesenchymal and adrenergic regulatory networks converging on distinct super-enhancer modules. Overall, this study reveals subtype-specific super-enhancer regulation in NBs.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neuroblastoma
Tipo de estudio:
Prognostic_studies
Límite:
Child
/
Humans
Idioma:
En
Revista:
Nat Cancer
Año:
2021
Tipo del documento:
Article
País de afiliación:
Alemania