Forty-five patient-derived xenografts capture the clinical and biological heterogeneity of Wilms tumor
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 20, 2019
- Source ID
- 10.1038/s41467-019-13646-9
Entities
People
- Andrew J Murphy
- Andrew M. Davidoff
- Catherine A. Billups
- Christopher L. Morton
- Emilia Modolo Pinto
- Geoffrey Neale
- Gerard P Zambetti
- Heather Mulder
- Hyea Jin Gil
- Jeffrey S Dome
- Jerold E. Rehg
- Jinghui Zhang
- John Easton
- Justin S. Williams
- Lei Shi
- Mary A. Woolard
- Matthew L. Harlow
- Michael R Clay
- Peter J. Houghton
- Rani E. George
- Stanley Pounds
- Tong Lin
- Xiang Chen
- Xueyuan Cao
Organizations
- American Lebanese Syrian Associated Charities
- National Cancer Institute
- United States Department of Defense
- United States Department of Health and Human Services