DNA methylation of normal kidney, Wilms tumor and metastatic (lung) samples
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ABSTRACT:
PROVIDER: PRJNA685844 | ENA |
REPOSITORIES: ENA
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Project description:To identify underlying mechanisms involved with metastasis formation in Wilms tumors (WTs), we performed comprehensive DNA methylation and gene expression analyses of matched normal kidney (NK), WT blastemal component, and metastatic tissues (MT) from patients treated under SIOP 2001 protocol. A linear Bayesian framework model identified 497 differentially methylated positions (DMPs) between groups that discriminated NK from WT, but MT samples were divided in two groups. Accordingly, methylation variance grouped NK and three MT samples tightly together and all WT with four MT samples that showed high variability. WT were hypomethylated compared to NK, and MT had a hypermethylated pattern compared to both groups. The methylation patterns were in agreement with methylases and demethylases expression. Methylation data pointed to the existence of two groups of metastases. While hierarchical clustering analysis based on the expression of all 2569 differentially expressed genes (DEGs) discriminated WT and MT from all NK samples, the hierarchical clustering based on the expression of 44 genes with a differentially methylated region (DMR) located in their promoter region revealed two groups: one containing all NKs and three MTs and one containing all WT and four MTs. Methylation changes might be controlling expression of genes associated with WT progression. The 44 genes are candidates to be further explored as a signature for metastasis formation in WT.
2020-12-17 | GSE163372 | GEO
Project description:Genome wide DNA methylation profiling of normal kidney (n=36), nephrogenic rest (n=22) and Wilms tumour (n=37) was performed using the Illumina 450k array. Two papers were composed after analysis of this data (1) describes comparative analysis of 22 matched normal kidney-Wilms tumour pairs which identified biomarker differentially methylated regions (DMRs) that could be detected in patient blood; (2) describes comparative analysis of 20 matched trios which identified changes in methylation associated with progression from the precursor lesion towards tumourigenesis. Bisulfte converted DNA from 95 samples of normal kidney, nephrogenic rest and Wilms tumour was hybridised to Illumina HumanMethylation450 bead chips.
2014-07-08 | E-GEOD-59157 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling of normal kidney (n=36), nephrogenic rest (n=22) and Wilms tumour (n=37) was performed using the Illumina 450k array. Two papers were composed after analysis of this data (1) describes comparative analysis of 22 matched normal kidney-Wilms tumour pairs which identified biomarker differentially methylated regions (DMRs) that could be detected in patient blood; (2) describes comparative analysis of 20 matched trios which identified changes in methylation associated with progression from the precursor lesion towards tumourigenesis.
2014-07-08 | GSE59157 | GEO
Project description:The IGF2-intronic miR-483 selectively enhances transcription from IGF2 fetal promoters and enhances tumorigenesis. The expression levels of microRNAs were profiled in 20 human Wilms tumor samples (WT), 3 human normal adult kidney samples (AK) and 5 human fetal kidney samples (FK) using a Luminex bead platform.
2013-12-22 | E-GEOD-50505 | biostudies-arrayexpress
Project description:Wilms tumor (nephroblastoma) is a pediatric kidney tumor that arises from renal progenitor cells. Since the blastemal type is associated with adverse prognosis, we characterized such Wilms tumors by exome and transcriptome analysis. We detected novel, recurrent somatic mutations affecting the SIX1/2 – SALL1 pathway implicated in kidney development, the DROSHA/DGCR8 microprocessor genes as well as alterations in MYCN and TP53, the latter being strongly associated with dismal outcome. The DROSHA mutations impair the RNase III domains, while DGCR8 exhibits stereotypic E518K mutations in the RNA binding domain - both may skew miRNA representation. SIX1 and SIX2 mutations affect a single hotspot (Q177R) in the homeodomain indicative of a dominant effect. In larger cohorts, these mutations cluster in blastemal and chemotherapy-induced regressive tumors that likely derive from blastemal cells and these are characterized by generally higher SIX1/2 expression. These findings broaden the spectrum of human cancer genes and may open new avenues for stratification and therapeutic leads for Wilms tumors.
2015-02-18 | GSE53224 | GEO
Project description:Purpose: The 10x Genomics Visium platform allows us to define the spatial topography of gene expression and provides detailed molecular maps that overcome limitations associated with sn/scRNA-seq and microscopy-based spatial transcriptomics methods. The goals of this study are to compare and identify unique transcriptome profiling (RNA-seq) signature between unfavorable and favorable Wilms Tumors and against human fetal kidney. Methods: Human fetal kidney and Wilms tumor spatial topography of gene expression were generated using the 10X Visium platform Results: Using an optimized data analysis workflow, we mapped the reads to the hg38 genome build and grouped the spots into 9 clusters based on gene expression profiles. Conclusion: Our study represents the first implement of Visium technology in human fetal kidney and Wilms Tumor tissue, providing a number of important functional insights about the spatial and molecular definitions of cell populations across human fetal kidney and different subtypes of Wilms Tumor through analyzing gene expression within the intact spatial organization of the human samples.
2023-07-01 | GSE178349 | GEO
Project description:Wilms tumor (nephroblastoma) is a pediatric kidney tumor that arises from renal progenitor cells. Since the blastemal type is associated with adverse prognosis, we characterized such Wilms tumors by exome and transcriptome analysis. We detected novel, recurrent somatic mutations affecting the SIX1/2 – SALL1 pathway implicated in kidney development, the DROSHA/DGCR8 microprocessor genes as well as alterations in MYCN and TP53, the latter being strongly associated with dismal outcome. The DROSHA mutations impair the RNase III domains, while DGCR8 exhibits stereotypic E518K mutations in the RNA binding domain - both may skew miRNA representation. SIX1 and SIX2 mutations affect a single hotspot (Q177R) in the homeodomain indicative of a dominant effect. In larger cohorts, these mutations cluster in blastemal and chemotherapy-induced regressive tumors that likely derive from blastemal cells and these are characterized by generally higher SIX1/2 expression. These findings broaden the spectrum of human cancer genes and may open new avenues for stratification and therapeutic leads for Wilms tumors. 53 Wilms tumor samples were selected for RNA extraction and hybridization on Affymetrix Affymetrix Human Genome U133 Plus 2.0 Arrays.
2015-02-18 | E-GEOD-53224 | biostudies-arrayexpress
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
Project description:The aim of the study was to identify differentially expressed miRNAs in different Wilms tumor subtypes. Comparison of miRNA expression profiles in Wilms tumor of different subtypes (total n=62) compared to normal kidney tissue (n=4)
2015-02-11 | E-GEOD-57370 | biostudies-arrayexpress
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. Data represent examination of genome-wide chromatin modifications in primary Wilms tumors, fetal and mature kidney.
2010-05-05 | E-GEOD-20512 | biostudies-arrayexpress