Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design

Cell Rep. 2019 Nov 5;29(6):1675-1689.e9. doi: 10.1016/j.celrep.2019.09.071.


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.

Keywords: classifier; copy number profiling; patient-derived xenograft; pediatric cancer; preclinical testing; relapse; transcriptome sequencing; whole-exome sequencing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Central Nervous System Neoplasms / genetics*
  • Central Nervous System Neoplasms / metabolism
  • Child
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Exome Sequencing
  • Genomics
  • Humans
  • Mice
  • Mutation
  • Neuroblastoma / genetics
  • Neuroblastoma / metabolism
  • Neurofibromin 1 / antagonists & inhibitors*
  • Neurofibromin 1 / genetics
  • Neurofibromin 1 / metabolism
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Recurrence
  • Rhabdomyosarcoma / genetics
  • Rhabdomyosarcoma / metabolism
  • Sarcoma, Ewing / genetics
  • Sarcoma, Ewing / metabolism
  • Tumor Suppressor Protein p53 / antagonists & inhibitors*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Wilms Tumor / genetics
  • Wilms Tumor / metabolism
  • Xenograft Model Antitumor Assays*


  • NF1 protein, human
  • Neurofibromin 1
  • TP53 protein, human
  • Tumor Suppressor Protein p53