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.
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.
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
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.
Project description:We have carried out microarray-based comparative genomic hybridisation (arrayCGH) on 50 perilobar nephrogenic rest and 25 matching Wilms tumours in order to identify changes in DNA copy number associated with IGF-driven Wilms tumorigenesis. All patient samples were formalin fixed-paraffin embedded archival material. Tumour DNA was co-hybridised with normal female genomic DNA onto 5.8K, 0.9Mb-spaced (E-MEXP-213) and/or a 16K, 100kb-spaced BAC array. Data was normalised and quality-filtered, an adapted weights smoothing algorithm fitted, and changes in DNA copy number assessed for each clone.
Project description:In order to get a better insight into the timing of WT1 mutant Wilms tumor development, we compared the gene expression profiles of nine established WT1 mutant Wilms tumor cell lines with published data from different kidney cell types during development. Publications describing genes expressed in nephrogenic precursor cells, ureteric bud cells, more mature nephrogenic epithelial cells and interstitial cell types were used. These studies uncovered that the WT1 mutant Wilms tumor cells lines express genes from the earliest nephrogenic progenitor cells, as well as from more differentiated nephron cells with the highest expression from the stromal/interstitial compartment. The expression of genes from all cell compartments points to an early developmental origin of the tumor in a common stem cell. Although variability of the expression of specific genes was evident between the cell lines the overall expression pattern was very similar. This is likely dependent on their different genetic backgrounds with distinct WT1 mutations and the absence/presence of mutant CTNNB1.
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.
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)
