RPS6KA4/MIR1237 and AURKC promoter regions are differentially methylated in Wilms' tumor.

In this study, the DNA methylation profile of WT was characterized with Beadchip array. Comparisons between WT with normal kidney identified 827 differentially methylated regions, most of which were attributable in hypermethylation in CpG islands. Among affected genes, WT1 and TP73 showed altered enhancers where hypermethylation was validaded by pyrosequencing. Thirty differentially methylated regions (DMRs) were identified in WT as compared to normal kidney, two of which were previously described. Two novel DMRs, located in RPS6KA4/MIR1237 and the AURKC promoter, were found to be hypermethylated in WT. Altogether, our data reinforced the relevance of alterations of DNA methylation in WT, highlighting the complex nature of these alterations that affect promoter regions as well as enhancers, UTRs and gene bodies. PMID: 28930610 [PubMed - in process]
Source: Frontiers in Bioscience - Elite - Category: Biomedical Science Tags: Front Biosci (Elite Ed) Source Type: research

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(Wellcome Trust Sanger Institute) A fundamental change in our understanding of the childhood kidney cancer Wilms' tumor is on the horizon, after the discovery of its earliest genetic root by scientists at the Wellcome Sanger Institute and their collaborators. By comparing genome sequences from normal kidney tissue and tumors, the team identified patches of normal-looking kidney tissue that in fact carried DNA changes that cause Wilms' tumor.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
Adult cancers often arise from premalignant clonal expansions. Whether the same is true of childhood tumors has been unclear. To investigate whether Wilms tumor (nephroblastoma; a childhood kidney cancer) develops from a premalignant background, we examined the phylogenetic relationship between tumors and corresponding normal tissues. In 14 of 23 cases studied (61%), we found premalignant clonal expansions in morphologically normal kidney tissues that preceded tumor development. These clonal expansions were defined by somatic mutations shared between tumor and normal tissues but absent from blood cells. We also found hyper...
Source: ScienceNOW - Category: Science Authors: Tags: Development, Medicine, Diseases reports Source Type: news
Wilms tumor (WT) is the most common childhood kidney cancer globally. Our prior unbiased proteomic screen of WT disparities revealed increased expression of Fragile X-Related 1 (FXR1) in Kenyan specimens where survival is dismal. FXR1 is an RNA-binding protein that associates with poor outcomes in multiple adult cancers. The aim of this study therefore was to validate and characterize the FXR1 expression domain in WT.
Source: Journal of Pediatric Surgery - Category: Surgery Authors: Source Type: research
CONCLUSIONS: These data suggest that WT biology within a population of Iraqi children manifests features both similar to and unique from disease variants in other regions of the world. These observations will help to risk stratify WT patients living in this difficult environment to more or less intensive therapies and to focus treatment on cell-specific targets. PMID: 30155617 [PubMed - as supplied by publisher]
Source: World Journal of Pediatrics : WJP - Category: Pediatrics Authors: Tags: World J Pediatr Source Type: research
Messenger RNA encodes cellular function and phenotype. In the context of human cancer, it defines the identities of malignant cells and the diversity of tumor tissue. We studied 72,501 single-cell transcriptomes of human renal tumors and normal tissue from fetal, pediatric, and adult kidneys. We matched childhood Wilms tumor with specific fetal cell types, thus providing evidence for the hypothesis that Wilms tumor cells are aberrant fetal cells. In adult renal cell carcinoma, we identified a canonical cancer transcriptome that matched a little-known subtype of proximal convoluted tubular cell. Analyses of the tumor compos...
Source: ScienceNOW - Category: Science Authors: Tags: Development, Medicine, Diseases reports Source Type: news
(Institute of Cancer Research) Genetic mutations in a gene called REST have been shown to cause Wilms tumor, a rare kidney cancer that occurs in children.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
Nature Genetics 47, 1471 (2015). doi:10.1038/ng.3440 Authors: Shazia S Mahamdallie, Sandra Hanks, Kristen L Karlin, Anna Zachariou, Elizabeth R Perdeaux, Elise Ruark, Chad A Shaw, Alexander Renwick, Emma Ramsay, Shawn Yost, Anna Elliott, Jillian Birch, Michael Capra, Juliet Gray, Juliet Hale, Judith Kingston, Gill Levitt, Thomas McLean, Eamonn Sheridan, Anthony Renwick, Sheila Seal, Charles Stiller, Neil Sebire, Thomas F Westbrook &Nazneen Rahman Wilms tumor is the most common childhood renal cancer. To identify mutations that predispose to Wilms tumor, we are conducting exome sequencing studies. Here we descri...
Source: Nature Genetics - Category: Genetics & Stem Cells Authors: Tags: Letter Source Type: research
Wilms tumor (WT) is the most common childhood kidney cancer worldwide and poses a cancer health disparity to black children of sub‐Saharan African ancestry. Although overall survival from WT at 5 years exceeds 90% in developed countries, this pediatric cancer is alarmingly lethal in sub‐Saharan Africa and specifically in Kenya (36% survival at 2 years). Although multiple barriers to adequate WT therapy contribute to this dismal outcome, we hypothesized that a uniquely aggressive and treatment‐resistant biology compromises survival further. To explore the biologic composition of Kenyan WT (KWT), we completed a next ge...
Source: Genes, Chromosomes and Cancer - Category: Cancer & Oncology Authors: Tags: Research Article Source Type: research
 In this email to our CEO, Bill Bro, Shannon Bell, Director, Office of Advocacy Relations, at the National Cancer Institute, describes new initiatives in kidney cancer research.  Mr. Bro will attend the National Cancer Advisory Board meetings, in Bethesda, in his capacity as a liaison representing cancer survivors.Dear Bill: I would like to take this opportunity to call your attention to several of NCI’s exciting initiatives funded through the American Recovery and Reinvestment Act of 2009 (ARRA) in both cancer research generally and in kidney cancer specifically. I am pleased to report that ...
Source: Kidney Cancer Association - Category: Urology & Nephrology Source Type: news
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