Cell Reports: Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design
Author links open overlay panelJo LynneRokita123 Komal S.Rathi23 Maria F.Cardenas4 Kristen A.Upton1 JoyJayaseelan4 Katherine L.Cross5 JacobPfeil6 Laura E.Egolf17 Gregory P.Way8 AlvinFarrel2 Nathan M.Kendsersky19 KhushbuPatel2 Krutika S.Gaonkar23 ApexaModi18 Esther R.Berko1 GonzaloLopez12 ZalmanVaksman2 ChelseaMayoh10 JonasNance11 KristynMcCoy11 MichelleHaber10 KathrynEvans10 HannahMcCalmont10 KaterinaBendak10 Julia W.Böhm10 Glenn M.Marshall1012 VanessaTyrrell13 KarthikKalletla23 Frank K.Braun14 LinQi1516 YunchenDu1516 HuiyuanZhang1516Holly B.Lindsay1516 SiboZhao1516JackShu1516 PatriciaBaxter1516 ChristopherMorton17 DiasKurmashev18 SiyuanZheng18 YidongChen18 JayBowen19 Anthony C.Bryan19 Kristen M.Leraas19 Sara E.Coppens19 HarshaVardhanDoddapaneni4 ZeineenMomin4 WendongZhang20 Gregory I.Sacks1 Lori S.Hart1 KaterynaKrytska1 Yael P.Mosse1 Gregory J.Gatto21 YolandaSanchez2223Casey S.Greene249Sharon J.Diskin12Olena MorozovaVaske256DavidHaussler626Julie M.Gastier-Foster1927E. AndersKolb2829RichardGorlick20Xiao-NanLi15163031C. PatrickReynolds11Raushan T.Kurmasheva18Peter J.Houghton18Malcolm A.Smith32Richard B.Lock13PichaiRaman23David A.Wheeler4John M.Maris133
Summary
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 the 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.
Since 2004, UT Health San Antonio, Greehey Children’s Cancer Research Institute’s (Greehey CCRI) mission has been to advance scientific knowledge relevant to childhood cancer, contribute to understanding its causes, and accelerate the translation of knowledge into novel therapies. Greehey CCRI strives to have a national and global impact on childhood cancer by discovering, developing, and disseminating new scientific knowledge. Our mission consists of three key areas — research, clinical, and education.
Stay connected with the Greehey CCRI on Facebook, Twitter, LinkedIn, and Instagram.