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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.

SUBMITTER: Murphy AJ

PROVIDER: S-EPMC6925259 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Murphy Andrew J AJ Chen Xiang X Pinto Emilia M EM Williams Justin S JS Clay Michael R MR Pounds Stanley B SB Cao Xueyuan X Shi Lei L Lin Tong T Neale Geoffrey G Morton Christopher L CL Woolard Mary A MA Mulder Heather L HL Gil Hyea Jin HJ Rehg Jerold E JE Billups Catherine A CA Harlow Matthew L ML Dome Jeffrey S JS Houghton Peter J PJ Easton John J Zhang Jinghui J George Rani E RE Zambetti Gerard P GP Davidoff Andrew M AM

Nature communications 20191220 1

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<sup>-/-</sup> 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 ...[more]

PMID: 31862972

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

Publications

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

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