RT Journal Article SR Electronic T1 Genomic profiling of childhood tumor patient-derived xenograft models to enable rational clinical trial design JF bioRxiv FD Cold Spring Harbor Laboratory SP 566455 DO 10.1101/566455 A1 Jo Lynne Rokita A1 Komal S. Rathi A1 Maria F. Cardenas A1 Kristen A. Upton A1 Joy Jayaseelan A1 Katherine L. Cross A1 Jacob Pfeil A1 Laura E. Ritenour A1 Apexa Modi A1 Alvin Farrel A1 Gregory P. Way A1 Nathan M. Kendsersky A1 Khushbu Patel A1 Gonzalo Lopez A1 Zalman Vaksman A1 Chelsea Mayoh A1 Jonas Nance A1 Kristyn McCoy A1 Michelle Haber A1 Kathryn Evans A1 Hannah McCalmont A1 Katerina Bendak A1 Julia W. Böhm A1 Glenn M. Marshall A1 Vanessa Tyrrell A1 Karthik Kalletla A1 Frank K. Braun A1 Lin Qi A1 Yunchen Du A1 Huiyuan Zhang A1 Holly B. Lindsay A1 Sibo Zhao A1 Jack Shu A1 Patricia Baxter A1 Christopher Morton A1 Dias Kurmashev A1 Siyuan Zheng A1 Yidong Chen A1 Jay Bowen A1 Anthony C. Bryan A1 Kristen M. Leraas A1 Sara E. Coppens A1 HarshaVardhan Doddapaneni A1 Zeineen Momin A1 Wendong Zhang A1 Gregory I. Sacks A1 Lori S. Hart A1 Kateryna Krytska A1 Yael P. Mosse A1 Gregory J. Gatto A1 Yolanda Sanchez A1 Casey S. Greene A1 Sharon J. Diskin A1 Olena Morozova Vaske A1 David Haussler A1 Julie M. Gastier-Foster A1 E. Anders Kolb A1 Richard Gorlick A1 Xiao-Nan Li A1 C. Patrick Reynolds A1 Raushan T. Kurmasheva A1 Peter J. Houghton A1 Malcolm A. Smith A1 Richard B. Lock A1 Pichai Raman A1 David A. Wheeler A1 John M. Maris YR 2019 UL http://biorxiv.org/content/early/2019/03/30/566455.abstract AB Accelerating cures for children with cancer remains an immediate challenge due to 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) from high-risk childhood cancers, many refractory to current standard-of-care treatments. Here, we genomically characterize 261 PDX models from 29 unique pediatric cancer malignancies and demonstrate faithful recapitulation of histologies, subtypes, and refine our understanding of relapsed disease. Expression and mutational signatures are used to classify tumors for TP53 and NF1 inactivation, as well as impaired DNA repair. We anticipate that these data will serve as a resource for pediatric oncology drug development and guide rational clinical trial design for children with cancer.HighlightsMultiplatform genomic analysis defines landscape of 261 pediatric cancer patient derived xenograft (PDX) modelsPediatric patient derived xenografts faithfully recapitulate relapsed diseaseInferred TP53 pathway inactivation correlates with pediatric cancer copy number burdenSomatic mutational signatures predict impaired DNA repair across multiple histologies