Project description:Children with favorable histology Wilms tumor (FHWT) who relapse or whose tumors show blastemal predominance post-chemotherapy often face poor outcomes. The purpose of this study is to identify mechanisms of chemotherapy resistance in FHWT. We induce a patient-derived xenograft model (KT-47) to develop blastemal predominance after chemotherapy and become resistant to vincristine, actinomycin-D, and doxorubicin (VAD). Multi-omics analyses reveal chromatin and transcriptional changes, including increased H3K4me3 and decreased H3K27me3 at stem cell and nephrogenesis gene loci. LIN28B is the most upregulated resistance-associated gene, linked to MYCN copy gain/upregulation and chromatin remodeling. ABCB1 expression correlates with inter-chromosomal enhancer interactions and functions as the mediator of chemotherapy resistance in vitro. These findings are validated in additional Wilms tumor models. Overall, resistance is associated with de-differentiation to a stem-like state and is driven ABCB1 upregulation, suggesting that therapeutic strategies targeting chromatin regulation and drug efflux may be relevant in therapy-resistant Wilms tumor.

2026-02-05 | MSV000100734 | MassIVE

Predicting Relapse in Favorable Histology Wilms Tumor Using Gene Expression

Project description:The gene expression patterns of favorable histology Wilms tumors (FHWT) that relapsed were compared with those that did not relapse using oligonucleotide arrays Description: 250 FHWT of all stages enriched for relapses treated on National Wilms Tumor Study 5 passed quality parameters and were suitable for analysis using oligonucleotide arrays. Relapse risk stratification utilized Support Vector Machine; two and ten fold cross-validation was applied. The number of genes associated with relapse was less than that predicted by chance alone for 106 patients (32 relapses) with stages I and II FHWT and no further analyses were performed. This number was greater than expected by chance for 76 local stage III patients. Cross validation including an additional 68 local stage III patients (total 144 patients, 53 relapses) demonstrated that classifiers for relapse composed of 50 genes were associated with a median sensitivity of 47%, specificity 70%, and total error rate of 38%. Analysis of genes differentially expressed in relapse patients revealed apoptosis, Wnt signaling, IGF pathway, and epigenetic modification to be mechanisms important in relapse. Potential therapeutic targets include FRAP/MTOR and CD40. Keywords: Classification by microarray analysis

2009-01-30 | GSE10320 | GEO

Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor

Project description:Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor

| PRJNA1269528 | ENA

Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor [HiC]

Project description:Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor [HiC]

| PRJNA1269535 | ENA

Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor [methylation]

Project description:Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor [methylation]

| PRJNA1269495 | ENA

Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor [CUT&Tag]

Project description:Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor [CUT&Tag]

| PRJNA1269531 | ENA

Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor [RNA-seq]

Project description:Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor [RNA-seq]

| PRJNA1269533 | ENA

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