Embryonal precursors of Wilms tumor.
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ABSTRACT:
SUBMITTER: Coorens THH
PROVIDER: S-EPMC6914378 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
Publications
Embryonal precursors of Wilms tumor.
Coorens Tim H H THH Treger Taryn D TD Al-Saadi Reem R Moore Luiza L Tran Maxine G B MGB Mitchell Thomas J TJ Tugnait Suzanne S Thevanesan Christine C Young Matthew D MD Oliver Thomas R W TRW Oostveen Minou M Collord Grace G Tarpey Patrick S PS Cagan Alex A Hooks Yvette Y Brougham Mark M Reynolds Ben C BC Barone Giuseppe G Anderson John J Jorgensen Mette M Burke G A Amos GAA Visser Johannes J Nicholson James C JC Smeulders Naima N Mushtaq Imran I Stewart Grant D GD Campbell Peter J PJ Wedge David C DC Martincorena Iñigo I Rampling Dyanne D Hook Liz L Warren Anne Y AY Coleman Nicholas N Chowdhury Tanzina T Sebire Neil N Drost Jarno J Saeb-Parsy Kourosh K Stratton Michael R MR Straathof Karin K Pritchard-Jones Kathy K Behjati Sam S
Science (New York, N.Y.) 20191201 6470
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 exp ...[more]
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Project description:BackgroundThe "fetal programming" hypothesis has been evaluated in many adult diseases including cancer, but not for Wilms tumor. Wilms tumor has been related to high birthweight, but little is known about other growth metrics such as a baby's birth length, ponderal index, or placenta size, which can shed additional light on growth patterns.MethodsCases of Wilms tumor (N = 217) were taken from the Danish Cancer Registry, and controls (N = 4340) were randomly selected from the Population Register and matched to cases by sex and age. Linkage to the Medical Births Registry provided information on gestational factors and fetal growth measurements, while linkage to the Patient Register provided information on maternal and child health conditions.ResultsDespite having typically normal to higher birthweights, Wilms tumor cases had smaller placentas (≤540 g; odds ratio (OR) = 4.24; 95% confidence interval (CI), 1.84-9.78) and a lower placenta-to-birthweight ratio (OR = 1.81; 95% CI, 1.17-2.82, per 1 SD decrease). Small placentas were more common among Wilms cases without congenital anomalies (OR = 6.43; 95% CI, 1.95-21.21). Wilms tumor cases had a higher prevalence of high birthweight (>4000 g; OR = 1.57; 95% CI, 1.11-2.22), birth length 55 cm or longer (OR = 1.74; 95% CI, 1.09-2.78), and being large for gestational age (OR = 1.79; 95% CI, 1.08-2.96).ConclusionsOur study corroborates earlier studies showing associations with high birthweight and suggests associations between Wilms tumor and decreased placental size and low placenta-to-birthweight ratio.
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Project description:Background/purposeWilms 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.MethodsQuantitative FXR1 gene expression was compared between WT, adjacent, adult, and fetal kidney specimens. The cellular and subcellular expression domain of FXR1 was characterized across these tissues using immunoperoxidase staining. RNA-sequencing of FXR1 was performed from WT and other pediatric malignancies to examine its broader target potential.ResultsFXR1 was detected in all clinical WT specimens evaluated (n = 82), and as a result appeared independent of demographic, histology, or adverse event. Specific cytosolic staining was strongest in blastema, intermediate and variable in epithelia, and weakest in stroma. When present, areas of skeletal muscle differentiation stained strongly for FXR1. qPCR revealed increased FXR1 expression in WT compared to adult and adjacent kidney (p < 0.0002) but was similar to fetal kidney (p = 0.648). RNA-sequencing revealed expression of FXR1 in multiple pediatric tumors, greatest in rhabdomyosarcoma and WT.ConclusionsFXR1 was expressed consistently across this broad sampling of WT and most robustly in the primitive blastema. Notably, FXR1 labeled a specific self-renewing progenitor population of the fetal kidney.
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Project description:Our study aimed to identify relevant transcriptomic biomarkers for the Wilms tumor, the most common pediatric kidney cancer, independent of the histological type and stage. Using next-generation sequencing, we analyzed the miRNA profiles of 74 kidney samples, which were divided into two independent groups: fresh frozen tissue and formalin-fixed paraffin-embedded tissue samples. Subsequent mRNA expression profiling and pathway analysis were performed to establish the interplay and potential involvement of miRNAs and mRNA in the Wilms tumor. Comparative analysis, irrespective of post-dissection tissue processing, revealed 41 differentially expressed miRNAs, with 27 miRNAs having decreased expression and 14 miRNAs having increased expression in the Wilms tumor tissue compared to healthy kidney tissue. Among global mRNA transcriptomic profile differences, cross-sectional analysis suggested a limited list of genes potentially regulated by differentially expressed miRNAs in the Wilms tumor. This study identified the comprehensive miRNA and mRNA profile of the Wilms tumor using next-generation sequencing and bioinformatics approach, providing better insights into the pathogenesis of the Wilms tumor. The identified Wilms tumor miRNAs have potential as biomarkers for the diagnosis and treatment of the Wilms tumor, regardless of histological subtype and disease stage.
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| S-EPMC9405781 | biostudies-literature