Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.
Animals
Cell Line, Tumor
Central Nervous System Neoplasms
/ genetics
Child
Clinical Trials as Topic
Disease Models, Animal
Genomics
Humans
Mice
Mutation
Neuroblastoma
/ genetics
Neurofibromin 1
/ antagonists & inhibitors
Osteosarcoma
/ genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ genetics
Recurrence
Rhabdomyosarcoma
/ genetics
Sarcoma, Ewing
/ genetics
Tumor Suppressor Protein p53
/ antagonists & inhibitors
Exome Sequencing
Wilms Tumor
/ genetics
Xenograft Model Antitumor Assays
classifier
copy number profiling
patient-derived xenograft
pediatric cancer
preclinical testing
relapse
transcriptome sequencing
whole-exome sequencing
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
05 11 2019
05 11 2019
Historique:
received:
31
03
2019
revised:
10
07
2019
accepted:
24
09
2019
entrez:
7
11
2019
pubmed:
7
11
2019
medline:
25
9
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31693904
pii: S2211-1247(19)31268-9
doi: 10.1016/j.celrep.2019.09.071
pmc: PMC6880934
mid: NIHMS1542708
pii:
doi:
Substances chimiques
NF1 protein, human
0
Neurofibromin 1
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1675-1689.e9Subventions
Organisme : NCI NIH HHS
ID : U01 CA199288
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA199000
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA199287
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA220500
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA199222
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA199221
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA221957
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS095411
Pays : United States
Organisme : NCI NIH HHS
ID : L40 CA220942
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA263981
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009615
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA199297
Pays : United States
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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