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

对儿童肿瘤患者来源的异种移植模型进行基因组分析,以实现合理的临床试验设计

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作者:Jo Lynne Rokita, Komal S Rathi, Maria F Cardenas, Kristen A Upton, Joy Jayaseelan, Katherine L Cross, Jacob Pfeil, Laura E Egolf, Gregory P Way, Alvin Farrel, Nathan M Kendsersky, Khushbu Patel, Krutika S Gaonkar, Apexa Modi, Esther R Berko, Gonzalo Lopez, Zalman Vaksman, Chelsea Mayoh, Jonas Nance,

Abstract

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.

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