Embryonal precursors of Wilms tumor.
Science
; 366(6470): 1247-1251, 2019 12 06.
Article
en En
| MEDLINE
| ID: mdl-31806814
ABSTRACT
Adult cancers often arise from premalignant clonal expansions. Whether the same is true of childhood tumors has been unclear. To investigate whether Wilms tumor (nephroblastoma; a childhood kidney cancer) develops from a premalignant background, we examined the phylogenetic relationship between tumors and corresponding normal tissues. In 14 of 23 cases studied (61%), we found premalignant clonal expansions in morphologically normal kidney tissues that preceded tumor development. These clonal expansions were defined by somatic mutations shared between tumor and normal tissues but absent from blood cells. We also found hypermethylation of the H19 locus, a known driver of Wilms tumor development, in 58% of the expansions. Phylogenetic analyses of bilateral tumors indicated that clonal expansions can evolve before the divergence of left and right kidney primordia. These findings reveal embryonal precursors from which unilateral and multifocal cancers develop.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Lesiones Precancerosas
/
Células Clonales
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Tumor de Wilms
/
Metilación de ADN
/
Riñón
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Neoplasias Renales
Límite:
Child
/
Humans
Idioma:
En
Revista:
Science
Año:
2019
Tipo del documento:
Article
País de afiliación:
Reino Unido