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

Author

Listed:
  • Andrew J. Murphy

    (St. Jude Children’s Research Hospital
    University of Tennessee Health Science Center)

  • 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
    University of Tennessee Health Science Center)

  • 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
    University of Tennessee Health Science Center)

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.

Suggested Citation

  • 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, 2019. "Forty-five patient-derived xenografts capture the clinical and biological heterogeneity of Wilms tumor," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13646-9
    DOI: 10.1038/s41467-019-13646-9
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    Cited by:

    1. Andrew J. Murphy & Changde Cheng & Justin Williams & Timothy I. Shaw & Emilia M. Pinto & Karissa Dieseldorff-Jones & Jack Brzezinski & Lindsay A. Renfro & Brett Tornwall & Vicki Huff & Andrew L. Hong , 2023. "Genetic and epigenetic features of bilateral Wilms tumor predisposition in patients from the Children’s Oncology Group AREN18B5-Q," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Funan He & Abhik M. Bandyopadhyay & Laura J. Klesse & Anna Rogojina & Sang H. Chun & Erin Butler & Taylor Hartshorne & Trevor Holland & Dawn Garcia & Korri Weldon & Luz-Nereida Perez Prado & Anne-Mari, 2023. "Genomic profiling of subcutaneous patient-derived xenografts reveals immune constraints on tumor evolution in childhood solid cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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