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Gene expression data comparing Wilms tumor primary samples to patient-derived xenografts

ABSTRACT: The lack of model systems limits the preclinical testing of novel therapies to address Wilms tumor patient groups with poor outcomes. Therefore, we established 45 heterotopic Wilms tumor patient-derived xenografts (WTPDX) in CB17 scid-/- mice that capture the biological heterogeneity of Wilms tumor (WT). These WTPDX include six showing diffuse anaplasia, nine from patients who went on to experience disease relapse, and thirteen from patients with bilateral disease. WTPDX retained the genetic alterations and the global transcriptomic and methylation profile of corresponding primary WT. In addition, favorable histology WTPDX were chemosensitive, while unfavorable histology WTPDX were resistant to conventional chemotherapy with vincristine, actinomycin-D, and doxorubicin. This WTPDX library is a unique scientific resource that retains the spectrum of biological heterogeneity present in WT and provides an essential tool for the testing of novel targeted therapies in the era of precision medicine.

ORGANISM(S): Homo sapiens

PROVIDER: GSE110696 | GEO | 2019/02/14

REPOSITORIES: GEO

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DNA methylation data comparing Wilms tumor primary samples to patient-derived xenografts

Project description:The lack of model systems limits the preclinical testing of novel therapies to address Wilms tumor patient groups with poor outcomes. Therefore, we established 45 heterotopic Wilms tumor patient-derived xenografts (WTPDX) in CB17 scid-/- mice that capture the biological heterogeneity of Wilms tumor (WT). These WTPDX include six showing diffuse anaplasia, nine from patients who went on to experience disease relapse, and thirteen from patients with bilateral disease. WTPDX retained the genetic alterations and the global transcriptomic and methylation profile of corresponding primary WT. In addition, favorable histology WTPDX were chemosensitive, while unfavorable histology WTPDX were resistant to conventional chemotherapy with vincristine, actinomycin-D, and doxorubicin. This WTPDX library is a unique scientific resource that retains the spectrum of biological heterogeneity present in WT and provides an essential tool for the testing of novel targeted therapies in the era of precision medicine.

2019-02-14 | GSE110697 | GEO

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

Project description:The lack of model systems has limited the preclinical testing of novel therapies for Wilms tumor (WT) patients who have poor outcomes. Herein, we established 45 heterotopic WT patient-derived xenografts (WTPDX) in CB17 scid-/- mice that capture the biological heterogeneity of Wilms tumor (WT). These WTPDX include 6 from patients with diffuse anaplasia, 9 from patients who later experienced disease relapse, and 13 from patients with bilateral disease. Early passage WTPDX showed enrichment of blastemal gene expression. Favorable histology WTPDX were chemosensitive, whereas unfavorable histology WTPDX were 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 novel targeted therapies in the era of precision medicine.

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Homo sapiens

Project description:TARGET: Kidney - Wilms Tumor (WT)

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The Wilms' tumor blastema propagating cell is a self-renewing committed epithelial stem cell

Project description:Recently the cancer stem cell (CSC) model has been put forward to describe how a subset of cells within the tumor is responsible for tumor growth and heterogeneity. Wilms' tumor (WT), the most common pediatric renal malignancy, arises from developmentally arrested early renal progenitors. WT NCAM1+ALDH1+ CSCs have been recently isolated and shown to localize to tumor blastema. Herein by generating 'blastema'-only WT xenografts composed solely by cells expressing the SIX2 and NCAM1 embryonic renal stem cell markers, we surprisingly show that sorted ALDH1+ WT CSCs are phenotypically not the earliest renal stem cells. Rather, gene expression and proteomic comparative analysis disclose a more differentiated self-renewing epithelial cell type than bulk of the blastema. Thus, WT CSCs do not represent the transformed counterpart of the most primitive renal stem cell being more differentiated than the presumable WT cell of origin and are likely to de-differentiate to propagate the tumor blastema. We used Wilms tumor Xns, as well as, fetal renal tissue originally obtained from a patients or aborted fetus

2015-12-31 | E-GEOD-57269 | biostudies-arrayexpress

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Transcriptomic Characterization of wilms tumor

Project description:Wilms tumor (WT) is the most common renal malignancy in children. So we aim to investigate the transcriptomic map of Wilms tumor.

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Single nuclear RNASeq Analysis of Anaplastic and Favourable Histology Hu_Wilms Tumor

Project description:Wilms tumor is the most common pediatric kidney cancer. The best predictor of clinical outcome for Wilms tumor patients is how their tumor looks under the microscope (histology). Usually, the resistant/anaplastic component of the tumor makes up only a fraction of the total number of cells in the cancer. A critical barrier to understanding therapeutic resistance in this disease is that studies performed to sequence the resistant component is diluted by the other components of the tumor.Therefore, the current proposal aims to using single-nuclear-RNA sequencing to isolate the gene expression patterns of individual cell types in Wilms tumor and to focus on the anaplastic/resistant cells.

2022-04-08 | GSE200256 | GEO

Prospective isolation and characterization of renal cancer stem cells from human Wilms' tumor xenografts leads to tumor eradication

Project description:Downregulation of specific microRNAs contribute to epithelial-mesenchymal transition of Wilms' tumor cancer initiating cells. In order to gain insight into the biology of initiating cells/cancer stem cells (CIC/CSCs) in Wilms' tumor, we compared the microRNA expression profile of un-sorted propagatable WT xenografts (p-WT Xn), p-WT NCAM+ALDH1+-derived Xn and human fetal kidneys (hFKs). Global microRNA expression analysis showed specific microRNAs to differentially express identifying a strong miRNA signature for the NCAM+ALDH1+ WT CICs.

2012-12-01 | GSE33332 | GEO

The Wilms' tumor blastema propagating cell is a self-renewing committed epithelial stem cell

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