A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor.
Cancer Cell
; 36(1): 51-67.e7, 2019 07 08.
Article
en En
| MEDLINE
| ID: mdl-31287992
ABSTRACT
Embryonal tumors with multilayered rosettes (ETMRs) are highly lethal infant brain cancers with characteristic amplification of Chr19q13.41 miRNA cluster (C19MC) and enrichment of pluripotency factor LIN28A. Here we investigated C19MC oncogenic mechanisms and discovered a C19MC-LIN28A-MYCN circuit fueled by multiple complex regulatory loops including an MYCN core transcriptional network and super-enhancers resulting from long-range MYCN DNA interactions and C19MC gene fusions. Our data show that this powerful oncogenic circuit, which entraps an early neural lineage network, is potently abrogated by bromodomain inhibitor JQ1, leading to ETMR cell death.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Cromosomas Humanos Par 19
/
Neoplasias Encefálicas
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Familia de Multigenes
/
Proteínas de Unión al ARN
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Neoplasias de Células Germinales y Embrionarias
/
MicroARNs
/
Proteína Proto-Oncogénica N-Myc
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cancer Cell
Asunto de la revista:
NEOPLASIAS
Año:
2019
Tipo del documento:
Article
País de afiliación:
Canadá