Similar Datasets
Project description:Children with favorable histology Wilms tumor (FHWT) who experience disease relapse or whose tumors exhibit blastemal predominance after chemotherapy often have poor outcomes. We established a FHWT patient-derived xenograft model, KT-47, that exhibited blastemal predominance after chemotherapy treatment with vincristine, actinomycin, and doxorubicin (VAD) and ultimately developed complete resistance to VAD after serial exposures to this combination. Histologic analyses and comprehensive multi-omics approaches were used to evaluate changes associated with resistance. CUT&TAG identified increased transcriptionally active H3K4me3 at stem cell and nephrogenesis gene promoters among the most different regions in KT-47 resistant compared to the KT-47 pretreatment model including the HOXB cluster, HOXC cluster, MYCN, SIX2, IGF2, CITED1, and OSR1. In contrast, decreased H3K27me3 was identified at HOX gene cluster and nephrogenesis gene promoter regions. The most significantly upregulated transcript and protein that associated with resistance in KT-47 was the let7 microRNA processor LIN28B. LIN28B upregulation was associated with copy number gain at MYCN and plasticity of cancer cells marked by open chromatin at the LIN28B locus rather than expansion of a minor subclone expressing LIN28B present in the original primary tumor material. The stem cell-associated multidrug resistance protein ABCB1 was upregulated in epithelial cells in association with an inter-chromosomal interaction between chromosomes 1 and 7. The impact of these findings at MYCN, LIN28B, and ABCB1 were validated in additional WT models and samples. Overall, these results support de-differentiation of FHWT cancer cells to a stem-like state which is associated with chemotherapy resistance. Targeting epigenetic modifiers that modulate differentiation of cancer cells with a stem-like phenotype could be a future treatment strategy in chemotherapy resistant FHWT.
2026-01-26 | GSE298482 | GEO
Project description:Children with favorable histology Wilms tumor (FHWT) who experience disease relapse or whose tumors exhibit blastemal predominance after chemotherapy often have poor outcomes. We established a FHWT patient-derived xenograft model, KT-47, that exhibited blastemal predominance after chemotherapy treatment with vincristine, actinomycin, and doxorubicin (VAD) and ultimately developed complete resistance to VAD after serial exposures to this combination. Histologic analyses and comprehensive multi-omics approaches were used to evaluate changes associated with resistance. CUT&TAG identified increased transcriptionally active H3K4me3 at stem cell and nephrogenesis gene promoters among the most different regions in KT-47 resistant compared to the KT-47 pretreatment model including the HOXB cluster, HOXC cluster, MYCN, SIX2, IGF2, CITED1, and OSR1. In contrast, decreased H3K27me3 was identified at HOX gene cluster and nephrogenesis gene promoter regions. The most significantly upregulated transcript and protein that associated with resistance in KT-47 was the let7 microRNA processor LIN28B. LIN28B upregulation was associated with copy number gain at MYCN and plasticity of cancer cells marked by open chromatin at the LIN28B locus rather than expansion of a minor subclone expressing LIN28B present in the original primary tumor material. The stem cell-associated multidrug resistance protein ABCB1 was upregulated in epithelial cells in association with an inter-chromosomal interaction between chromosomes 1 and 7. The impact of these findings at MYCN, LIN28B, and ABCB1 were validated in additional WT models and samples. Overall, these results support de-differentiation of FHWT cancer cells to a stem-like state which is associated with chemotherapy resistance. Targeting epigenetic modifiers that modulate differentiation of cancer cells with a stem-like phenotype could be a future treatment strategy in chemotherapy resistant FHWT.
2026-01-26 | GSE298463 | GEO
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
Project description:Children with favorable histology Wilms tumor (FHWT) who experience disease relapse or whose tumors exhibit blastemal predominance after chemotherapy often have poor outcomes. We established a FHWT patient-derived xenograft model, KT-47, that exhibited blastemal predominance after chemotherapy treatment with vincristine, actinomycin, and doxorubicin (VAD) and ultimately developed complete resistance to VAD after serial exposures to this combination. Histologic analyses and comprehensive multi-omics approaches were used to evaluate changes associated with resistance. CUT&TAG identified increased transcriptionally active H3K4me3 at stem cell and nephrogenesis gene promoters among the most different regions in KT-47 resistant compared to the KT-47 pretreatment model including the HOXB cluster, HOXC cluster, MYCN, SIX2, IGF2, CITED1, and OSR1. In contrast, decreased H3K27me3 was identified at HOX gene cluster and nephrogenesis gene promoter regions. The most significantly upregulated transcript and protein that associated with resistance in KT-47 was the let7 microRNA processor LIN28B. LIN28B upregulation was associated with copy number gain at MYCN and plasticity of cancer cells marked by open chromatin at the LIN28B locus rather than expansion of a minor subclone expressing LIN28B present in the original primary tumor material. The stem cell-associated multidrug resistance protein ABCB1 was upregulated in epithelial cells in association with an inter-chromosomal interaction between chromosomes 1 and 7. The impact of these findings at MYCN, LIN28B, and ABCB1 were validated in additional WT models and samples. Overall, these results support de-differentiation of FHWT cancer cells to a stem-like state which is associated with chemotherapy resistance. Targeting epigenetic modifiers that modulate differentiation of cancer cells with a stem-like phenotype could be a future treatment strategy in chemotherapy resistant FHWT.
2026-01-26 | GSE298479 | GEO
Project description:Children with favorable histology Wilms tumor (FHWT) who experience disease relapse or whose tumors exhibit blastemal predominance after chemotherapy often have poor outcomes. We established a FHWT patient-derived xenograft model, KT-47, that exhibited blastemal predominance after chemotherapy treatment with vincristine, actinomycin, and doxorubicin (VAD) and ultimately developed complete resistance to VAD after serial exposures to this combination. Histologic analyses and comprehensive multi-omics approaches were used to evaluate changes associated with resistance. CUT&TAG identified increased transcriptionally active H3K4me3 at stem cell and nephrogenesis gene promoters among the most different regions in KT-47 resistant compared to the KT-47 pretreatment model including the HOXB cluster, HOXC cluster, MYCN, SIX2, IGF2, CITED1, and OSR1. In contrast, decreased H3K27me3 was identified at HOX gene cluster and nephrogenesis gene promoter regions. The most significantly upregulated transcript and protein that associated with resistance in KT-47 was the let7 microRNA processor LIN28B. LIN28B upregulation was associated with copy number gain at MYCN and plasticity of cancer cells marked by open chromatin at the LIN28B locus rather than expansion of a minor subclone expressing LIN28B present in the original primary tumor material. The stem cell-associated multidrug resistance protein ABCB1 was upregulated in epithelial cells in association with an inter-chromosomal interaction between chromosomes 1 and 7. The impact of these findings at MYCN, LIN28B, and ABCB1 were validated in additional WT models and samples. Overall, these results support de-differentiation of FHWT cancer cells to a stem-like state which is associated with chemotherapy resistance. Targeting epigenetic modifiers that modulate differentiation of cancer cells with a stem-like phenotype could be a future treatment strategy in chemotherapy resistant FHWT.
2026-01-26 | GSE298478 | GEO
Project description:Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor
| PRJNA1269528 | ENA
Project description:Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor [methylation]
| PRJNA1269495 | ENA
Project description:Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor [HiC]
| PRJNA1269535 | ENA
Project description:Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor [CUT&Tag]
| PRJNA1269531 | ENA
Project description:Induction of a renal developmental cell state is associated with chemotherapy resistance in favorable-histology Wilms tumor [RNA-seq]
| PRJNA1269533 | ENA