Forty-five Patient-derived Xenografts Capture the Clinical and Biological Heterogeneity of Wilms Tumor

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Dec 22

PMID 31862972

Citations 23

Authors

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

Andrew M Davidoff

Affiliations

Soon will be listed here.

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.

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