Geometry of Gene Expression Space of Wilms' Tumors From Human Patients

Neoplasia : an International Journal for Oncology Research
Ariel TrinkTomer Kalisky

Abstract

Wilms' tumor is a pediatric malignancy that is thought to originate from faulty kidney development during the embryonic stage. However, there is a large variation between tumors from different patients in both histology and gene expression that is not well characterized. Here we use a meta-analysis of published microarray datasets to show that Favorable Histology Wilms' Tumors (FHWT's) fill a triangle-shaped continuum in gene expression space of which the vertices represent three idealized "archetypes". We show that these archetypes have predominantly renal blastemal, stromal, and epithelial characteristics and that they correlate well with the three major lineages of the developing embryonic kidney. Moreover, we show that advanced stage tumors shift towards the renal blastemal archetype. These results illustrate the potential of this methodology for characterizing the cellular composition of Wilms' tumors and for assessing disease progression.

Citations

Feb 2, 2019·Nature Reviews. Nephrology·Taryn Dora TregerSam Behjati
Nov 30, 2019·Nature Communications·Jean HausserUri Alon
Dec 22, 2019·Nature Communications·Andrew J MurphyAndrew M Davidoff
Feb 26, 2020·Nature Reviews. Cancer·Jean Hausser, Uri Alon
Dec 22, 2020·Molecular Biology and Evolution·Mengyi Sun, Jianzhi Zhang
Aug 18, 2021·Radiology Case Reports·Selim AhmedConstance Sat Lin Liew

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Datasets Mentioned

BETA
GSE10320

Methods Mentioned

BETA
PCA
Laser
flow cytometry
xenograft
xenografts

Software Mentioned

R
clusterProfiler R package
WGCNA package
VennDiagram
enrichPathway
enrichGO
simpleaffy
ParTI Matlab
enrichKEGG
R package

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