Forty-five patient-derived xenografts capture the clinical and biological heterogeneity of Wilms tumor

Andrew J. Murphy (), Xiang Chen, Emilia M. Pinto, Justin S. Williams, Michael R. Clay, Stanley B. Pounds, Xueyuan Cao, Lei Shi, Tong Lin, Geoffrey Neale, Christopher L. Morton, Mary A. Woolard, Heather L. Mulder, Hyea Jin Gil, Jerold E. Rehg, Catherine A. Billups, Matthew L. Harlow, Jeffrey S. Dome, Peter J. Houghton, John Easton, Jinghui Zhang, Rani E. George, Gerard P. Zambetti and Andrew M. Davidoff
Additional contact information
Andrew J. Murphy: St. Jude Children’s Research Hospital
Xiang Chen: St. Jude Children’s Research Hospital
Emilia M. Pinto: St. Jude Children’s Research Hospital
Justin S. Williams: St. Jude Children’s Research Hospital
Michael R. Clay: St. Jude Children’s Research Hospital
Stanley B. Pounds: St. Jude Children’s Research Hospital
Xueyuan Cao: St. Jude Children’s Research Hospital
Lei Shi: St. Jude Children’s Research Hospital
Tong Lin: St. Jude Children’s Research Hospital
Geoffrey Neale: St. Jude Children’s Research Hospital
Christopher L. Morton: St. Jude Children’s Research Hospital
Mary A. Woolard: St. Jude Children’s Research Hospital
Heather L. Mulder: St. Jude Children’s Research Hospital
Hyea Jin Gil: St. Jude Children’s Research Hospital
Jerold E. Rehg: St. Jude Children’s Research Hospital
Catherine A. Billups: St. Jude Children’s Research Hospital
Matthew L. Harlow: Harvard Medical School
Jeffrey S. Dome: Children’s National Medical Center
Peter J. Houghton: University of Texas Health Science Center
John Easton: St. Jude Children’s Research Hospital
Jinghui Zhang: St. Jude Children’s Research Hospital
Rani E. George: Harvard Medical School
Gerard P. Zambetti: St. Jude Children’s Research Hospital
Andrew M. Davidoff: St. Jude Children’s Research Hospital

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract The lack of model systems has limited the preclinical discovery and testing of therapies for Wilms tumor (WT) patients who have poor outcomes. Herein, we establish 45 heterotopic WT patient-derived xenografts (WTPDX) in CB17 scid-/- mice that capture the biological heterogeneity of Wilms tumor (WT). Among these 45 total WTPDX, 6 from patients with diffuse anaplastic tumors, 9 from patients who experienced disease relapse, and 13 from patients with bilateral disease are included. Early passage WTPDX show evidence of clonal selection, clonal evolution and enrichment of blastemal gene expression. Favorable histology WTPDX are sensitive, whereas unfavorable histology WTPDX are resistant to conventional chemotherapy with vincristine, actinomycin-D, and doxorubicin given singly or in combination. This WTPDX library is a unique scientific resource that retains the spectrum of biological heterogeneity present in WT and provides an essential tool to test targeted therapies for WT patient groups with poor outcomes.

Date: 2019
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DOI: 10.1038/s41467-019-13646-9

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