Wilms Tumor cells with WT1 mutations have characteristic features of mesenchymal stem cells

ABSTRACT: Wilms tumors are genetically heterogeneous kidney tumors whose cells of origin are unknown. Tumors with WT1 mutations and concomitant loss of the wild-type allele represent a distinct subgroup, frequently associated with mutations in CTNNB1. Here we describe the establishment and characterization of long-term cell cultures derived from five individual Wilms tumors with WT1 mutations. Three of these tumor cell lines also had CTNNB1 mutations and an activated canonical Wnt signaling pathway as measured by β-catenin/TCF transcriptional activity. Four of the five Wilms cell lines had a stable normal karyotype for at least 25 passages, and four lines showed loss of heterozygosity of chromosome 11p due to mitotic recombination in 11p11. Gene expression profiling revealed that the Wilms tumor cell lines are highly similar to human mesenchymal stem cells (MSCs) and FACS analysis demonstrated expression of MSC-specific surface proteins CD105, CD90 and CD73. The stem cell like nature of the Wilms tumor cells is further supported by their adipogenic, chondrogenic, osteogenic and myogenic differentiation potentials. By generating multipotent mesenchymal precursors from paraxial mesoderm (PAM) in tissue culture using embryonal stem cells, gene expression profiles of PAM and MSCs were described. Using these published gene sets we found coexpression of a large number of genes in Wilms tumor cell lines, PAM and MSCs. Lineage plasticity is indicated by the simultaneous expression of genes from the mesendodermal and neuroectodermal lineages. We conclude that Wilms tumors with WT1 mutations have specific traits of PAM, which is the source of kidney stromal cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE18058 | GEO | 2010/02/01

SECONDARY ACCESSION(S): PRJNA119321

REPOSITORIES: GEO