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Somatic development of Wilms tumour via normal kidneys in predisposed children

ABSTRACT: Somatic development of Wilms tumour via normal kidneys in predisposed children

PROVIDER: PRJNA1241825 | ENA |

REPOSITORIES: ENA

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Somatic development of Wilms tumour via normal kidneys in predisposed children

Project description:Ten percent of children with cancer harbour a mutation in a predisposition gene. In children with the kidney cancer, Wilms tumour, the prevalence is as high as 30%. Certain predispositions are associated with defined histological and clinical features, suggesting differences in tumourigenesis. To investigate this, we assembled a cohort of 137 children with Wilms tumour, of whom 71 had a pathogenic germline or mosaic variant. We examined 237 neoplasms (including two secondary leukaemias) from the cohort, utilising whole genome sequencing, RNA sequencing and genome wide methylation, validating our findings in an independent cohort of 21 children. The development of tumours differed between children with sporadic disease and amongst those with a predisposition, depending on the variant gene and its developmental timing. Differences pervaded the repertoire of driver events, including high risk mutations, the clonal architecture of normal kidneys, and the relatedness of neoplasms from the same individual. Predisposition constrains Wilms tumourigenesis, suggesting a variant specific approach to managing these children merits consideration.

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Project description:Frequent long-range epigenetic silencing of protocadherin gene clusters on chromosome 5q31 in Wilms' tumour The data consists of five microarrays hybridized with methylated DNA immunoprecipitated from Wilms' tumours and from a normal foetal kidney control

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The developmental programme for genesis of the entire kidney is recapitulated in Wilms tumour

Project description:Expression profiling of Wilms tumour samples, which identified molecular signatures of the ureteric bud and collecting duct as well as those of the proximal and distal tubules in triphasic histology tumours. These observations indicate Wilms tumours can arise from a precursor cell capable of generating the entire kidney, such as the cells of the intermediate mesoderm from which both the metanephric mesenchym and ureteric bud are derived.

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Project description:The global gene expression pattern of Wilms tumors in comparison with clear cell sarcoma of the kidney (CCSK) and non-neoplastic fetal and adult kidneys.

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Project description:The Wilms' tumour 1 transcription factor regulates epigenetic states via DNA methyltransferase 3A. The data consists of two Nimblegen promoter/CpG island microarrays hybridized with MCIP DNA immunoprecipitated from either a HEK293-derived cell line expressing a heterologous WT1 cDNA (W210) or a control cell line containing the expression vector (IP100), both hybridized against input DNA.

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Lin28 sustains early renal progenitors and induces Wilms tumor

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