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Characterization of Alternative Splicing in High-Risk Wilms' Tumors. | LitMetric

Characterization of Alternative Splicing in High-Risk Wilms' Tumors.

Int J Mol Sci

Faculty of Engineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat Gan 5290002, Israel.

Published: April 2024

AI Article Synopsis

Article Abstract

The significant heterogeneity of Wilms' tumors between different patients is thought to arise from genetic and epigenetic distortions that occur during various stages of fetal kidney development in a way that is poorly understood. To address this, we characterized the heterogeneity of alternative mRNA splicing in Wilms' tumors using a publicly available RNAseq dataset of high-risk Wilms' tumors and normal kidney samples. Through Pareto task inference and cell deconvolution, we found that the tumors and normal kidney samples are organized according to progressive stages of kidney development within a triangle-shaped region in latent space, whose vertices, or "archetypes", resemble the cap mesenchyme, the nephrogenic stroma, and epithelial tubular structures of the fetal kidney. We identified a set of genes that are alternatively spliced between tumors located in different regions of latent space and found that many of these genes are associated with the epithelial-to-mesenchymal transition (EMT) and muscle development. Using motif enrichment analysis, we identified putative splicing regulators, some of which are associated with kidney development. Our findings provide new insights into the etiology of Wilms' tumors and suggest that specific splicing mechanisms in early stages of development may contribute to tumor development in different patients.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11050615PMC
http://dx.doi.org/10.3390/ijms25084520DOI Listing

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