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Cell Rep ; 29(6): 1675-1689.e9, 2019 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-31693904

RESUMEN

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer.


Asunto(s)
Neoplasias del Sistema Nervioso Central/genética , Neurofibromina 1/antagonistas & inhibidores , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteína p53 Supresora de Tumor/antagonistas & inhibidores , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Línea Celular Tumoral , Neoplasias del Sistema Nervioso Central/metabolismo , Niño , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Genómica , Humanos , Ratones , Mutación , Neuroblastoma/genética , Neuroblastoma/metabolismo , Neurofibromina 1/genética , Neurofibromina 1/metabolismo , Osteosarcoma/genética , Osteosarcoma/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Recurrencia , Rabdomiosarcoma/genética , Rabdomiosarcoma/metabolismo , Sarcoma de Ewing/genética , Sarcoma de Ewing/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Secuenciación del Exoma , Tumor de Wilms/genética , Tumor de Wilms/metabolismo
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