Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chromatin Analysis of Wilms Tumor Highlights Stem Cell Properties and a Renal Developmental Network

ABSTRACT: Wilms tumors are pediatric cancers thought to arise from kidney-specific stem cells. In order to identify transcriptional and epigenetic mechanisms that drive these malignant cells, we compared genomewide chromatin profiles of Wilms tumors to embryonic stem (ES) cells and normal kidney. Data represent examination of genome-wide chromatin modifications in primary Wilms tumors, fetal and mature kidney.

ORGANISM(S): Homo sapiens

SUBMITTER: Noam Shoresh

PROVIDER: E-GEOD-20512 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

CCSK

Project description:Clear cell sarcoma of the kidney (CCSK), the second most common renal tumor in children, poses significant diagnostic challenges. No diagnostic positive markers are available, and the pathogenesis of CCSK remains an enigma. To address these challenges, the gene expression patterns of fourteen CCSKs were compared to fifteen Wilms tumors (WT) and three fetal kidney samples using oligonucleotide arrays. Keywords: other. This dataset is part of the TransQST collection.

2005-09-22 | E-GEOD-2712 | biostudies-arrayexpress

Classification of a frameshift/extended and a stop mutation in WT1 as gain of function mutations which activate cell cycle genes and promote Wilms tumor cell proliferation

Project description:The Wilms tumor 1 (WT1) gene encodes a zinc finger transcription factor important for normal kidney development. WT1 is a suppressor for Wilms tumor development and an oncogene for diverse malignant tumors. We recently established cell lines from primary Wilms tumors and identified the corresponding WT1 mutations (see GSE18058). To investigate the function of mutant WT1 proteins we performed WT1 knockdown experiments in primary Wilms tumor cell lines with a frameshift/extension (p.V432fsX87 = Wilms3) and a stop mutation (p.P362X = Wilms2) of WT1, followed by genome wide gene expression analysis. A detailed analysis of these gene expression data using MetaCore enabled us to classify the WT1 mutations as gain of function mutations. The mutant WT1Wilms2 and WT1Wilms3 proteins acquired an ability to modulate the expression of a highly significant number of genes from the G2/M phase of the cell cycle, and WT1 knockdown experiments showed that they are required for Wilms tumor cell proliferation. Data from the literature show that p53 negatively regulates the activity of a large number of these genes which are also part of a core proliferation cluster in diverse human cancers. Our data strongly suggest that mutant WT1 proteins facilitate expression of these cell cycle genes by antagonizing transcriptional repression mediated by p53. In light of this it is important to note that mutant WT1 has an ability to physically interact with the tumor suppressor p53. Together the findings show for the first time, that mutant WT1 proteins have a gain of function and act as oncogenes for Wilms tumor development by regulating Wilms tumor cell proliferation. siWT1 mediated knockdown in two Wilms tumor cell lines one and two days after transfection versus non-silencing controls

2014-05-12 | E-GEOD-54635 | biostudies-arrayexpress

Retinoic acid pathway activity in Wilms tumors and characterization of biological responses in vitro

Project description:Wilms tumor (WT) is one of the most common malignancies in childhood. With current therapy protocols up to 90 % of patients can be cured, but there is still a need to improve therapy for patients with aggressive WT and to reduce treatment intensity where possible. Prior data suggested deregulation of the retinoic acid (RA) pathway in high-risk WT. This could be validated in a large independent tumor set. Reduced RA pathway activity and MYCN overexpression were found in high risk tumors as opposed to tumors with low/intermediate risk, suggesting a beneficial impact of RA on advanced WT. To investigate the possible mode of action of retinoids as a novel therapeutic agent we treated primary tumor cell cultures with all-trans-RA (ATRA), 9cis-RA, fenretinide and combinations of retinoids and a histone deacetylase (HDAC) inhibitor. Genes deregulated in high risk tumors showed opposite changes upon treatment suggesting a positive effect of retinoids. 6/7 primary cultures tested reduced proliferation, irrespective of prior RA signaling levels. The only variant culture was derived from mesoblastic nephroma, a distinct childhood kidney neoplasm. Retinoid / HDAC inhibitor combinations provided no synergistic effect. ATRA and 9cis-RA induced morphological changes suggestive of differentiation, while fenretinide induced apoptosis in several cultures tested. Microarray analysis of ATRA treated WT cells revealed differential expression of many genes involved in extracellular matrix formation and osteogenic, neuronal or muscle differentiation. Although some of the effects appear to be reversible, these findings provide further evidence of a potential utility of retinoids in Wilms tumor treatment. total samples analysed are 2

2012-04-20 | E-GEOD-28807 | biostudies-arrayexpress

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

Chromatin Analysis of Wilms Tumor Highlights Stem Cell Properties and a Renal Developmental Network

Project description:Wilms tumors are pediatric cancers thought to arise from kidney-specific stem cells. In order to identify transcriptional and epigenetic mechanisms that drive these malignant cells, we compared genomewide chromatin profiles of Wilms tumors to embryonic stem (ES) cells and normal kidney.

2010-05-05 | GSE20512 | GEO

Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis in Wilms tumors

Project description:Through whole-exome sequencing we identified somatic missense mutations in DICER1 and DROSHA in Wilms tumor, a childhood kidney cancer. DICER1 and DROSHA are key enzymes in the microRNA biogenesis pathway. To determine the effect of these mutations on microRNA expression, we prepared small RNAs from Wilms tumors and used next-generation sequencing to determine the expression levels of microRNAs in the tumors. Comparison of miRNA expression in tumors with and without mutations in DICER1 or DROSHA.

2015-04-21 | E-GEOD-56955 | biostudies-arrayexpress

Microarray analaysis of adult and childhood renal tumors.

Project description:Analysis of adult and childhood tumors reveals activation of an E2F3 signature unique to Wilms tumors. Keywords: Disease state analysis Clear cell, chromophobe, papillary (types 1 and 2), oncocytoma, and Wilms tumor were compared to normal kidney tissue. No technical replicates.

2008-06-05 | E-GEOD-11024 | biostudies-arrayexpress

Lin28 sustains early renal progenitors and induces Wilms tumor

Project description:Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of terminal differentiation of the embryonic kidney. Here we show that over-expression of the heterochronic regulator Lin28 during kidney development in mice markedly expands nephrogenic progenitors by blocking their final wave of differentiation, ultimately resulting in pathology highly reminiscent of Wilms tumor. Gene expression analysis was performed on a total of 8 kidneys samples, including 4 tumors samples from Lin28 transgenic mice and 4 control kidneys

2014-06-01 | E-GEOD-56323 | biostudies-arrayexpress

Homo sapiens

Project description:microRNA Profiling in Wilms Tumors and Kidney Tissues

| PRJNA217783 | ENA

Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis in Wilms tumors

2015-04-21 | GSE56955 | GEO