Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design
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.
The data in this datascope belong to the manuscript:
Rokita JL, Rathi KS, Cardenas MF, Upton KA, Jayaseelan J, Cross KL, Pfeil J, Egolf LE, Way GP, Farrel A, Kendsersky NM, Patel K, Gaonkar KS, Modi A, Berko ER, Lopez G, Vaksman Z, Mayoh C, Nance J, McCoy K, Haber M, Evans K, McCalmont H, Bendak K, Bohm JW, Marshall GM, Tyrrell V, Kalletla K, Braun FK, Qi L, Du Y, Zhang H, Lindsay HB, Zhao S, Shu J, Baxter P, Morton C, Kurmashev D, Zheng S, Chen Y, Bowen J, Bryan AC, Leraas KM, Coppens SE, Doddapaneni H, Momin Z, Zhang W, Sacks GI, Hart LS, Krytska K, Mosse YP, Gatto GJ, Sanchez Y, Greene CS, Diskin SJ, Vaske OM, Haussler D, Gastier-Foster JM, Kolb EA, Gorlick R, Li XN, Reynolds CP, Kurmasheva RT, Houghton PJ, Smith MA, Lock RB, Raman P, Wheeler DA, Maris JM, (2019). Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design. Cell Rep 29:1675-1689.e9 doi |