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 EastonJinghui Zhang, Rani E. George, Gerard P. Zambetti, Andrew M. Davidoff

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number5806
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Murphy, A. J., Chen, X., Pinto, E. M., Williams, J. S., Clay, M. R., Pounds, S. B., Cao, X., Shi, L., Lin, T., Neale, G., Morton, C. L., Woolard, M. A., Mulder, H. L., Gil, H. J., Rehg, J. E., Billups, C. A., Harlow, M. L., Dome, J. S., Houghton, P. J., ... Davidoff, A. M. (2019). Forty-five patient-derived xenografts capture the clinical and biological heterogeneity of Wilms tumor. Nature communications, 10(1), [5806]. https://doi.org/10.1038/s41467-019-13646-9