Abstract
SUMMARYAccelerating 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.
Highlights
The patient-derived xenografts (PDXs) generation methods are described in the STAR Methods
We performed wholeexome sequencing (WES) on 240 childhood cancer PDX models, whole-transcriptome sequencing (RNA sequencing [RNA-seq]) on 244 models, and SNP microarrays on 252 models (Figures 1 and S1; Table S1), and we performed short tandem repeat (STR) profiling on all 261 models (Table S2)
We found a significant correlation between the percent of human reads following WES hybrid mapping and the percent of human DNA in the tumor extract (Figure S1B; Pearson correlation R = 0.943, F = 272.5, df = 34, p value < 2.2eÀ16)
Summary
An estimated 15,780 children and adolescents (
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have