Wilms tumor chromatin profiles highlight stem cell properties and a renal developmental network.
Cell Stem Cell
; 6(6): 591-602, 2010 Jun 04.
Article
em En
| MEDLINE
| ID: mdl-20569696
ABSTRACT
Wilms tumor is the most common pediatric kidney cancer. To identify transcriptional and epigenetic mechanisms that drive this disease, we compared genome-wide chromatin profiles of Wilms tumors, embryonic stem cells (ESCs), and normal kidney. Wilms tumors prominently exhibit large active chromatin domains previously observed in ESCs. In the cancer, these domains frequently correspond to genes that are critical for kidney development and expressed in the renal stem cell compartment. Wilms cells also express "embryonic" chromatin regulators and maintain stem cell-like p16 silencing. Finally, Wilms and ESCs both exhibit "bivalent" chromatin modifications at silent promoters that may be poised for activation. In Wilms tumor, bivalent promoters correlate to genes expressed in specific kidney compartments and point to a kidney-specific differentiation program arrested at an early-progenitor stage. We suggest that Wilms cells share a transcriptional and epigenetic landscape with a normal renal stem cell, which is inherently susceptible to transformation and may represent a cell of origin for this disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromatina
/
Tumor de Wilms
/
Rim
/
Neoplasias Renais
/
Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Cell Stem Cell
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos