Comprehensive Biology and Genetics Compendium of Wilms Tumor Cell Lines with Different WT1 Mutations

Royer‐Pokora, Brigitte; Busch, Maike; Tenbusch, Sarah; Schmidt, Mathias; Beier, Manfred; Woods, Andrew D; Thiele, Holger; Mora, Jaume

doi:10.3390/cancers13010060

Cited by 14 publications

(12 citation statements)

References 32 publications

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“…When analyzing Wilms Tumor, we had no WT cell lines to directly compare the tumor samples with. A number of WT cells have recently been described 34 , and should be harmonized with existing data so researchers can evaluate for themselves how well these lines model primary tumor samples.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional fidelity enhances cancer cell line selection in pediatric cancers

Luck

Okimoto

et al. 2021

Preprint

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Multi-omic technologies have allowed for comprehensive profiling of patient-derived tumor samples and the cell lines that are intended to model them. Yet, our understanding of how cancer cell lines reflect native pediatric cancers in the age of molecular subclassification remains unclear and represents a clinical unmet need. Here we use Treehouse public data to provide an RNA-seq driven analysis of 799 cancer cell lines, focusing on how well they correlate to 1,655 pediatric tumor samples spanning 12 tumor types. For each tumor type we present a ranked list of the most representative cell lines based on correlation of their transcriptomic profiles to those of the tumor. We found that most (8/12) tumor types best correlated to a cell line of the closest matched disease type. We furthermore showed that inferred molecular subtype differences in medulloblastoma significantly impacted correlation between medulloblastoma tumor samples and cell lines. Our results are available as an interactive web application to help researchers select cancer cell lines that more faithfully recapitulate pediatric cancer.

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Section: Discussionmentioning

confidence: 99%

Transcriptional fidelity enhances cancer cell line selection in pediatric cancers

Luck

Okimoto

et al. 2021

Preprint

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“…Recent studies have shown the feasibility of generating short-term WT cell lines with limited genomic testing [14][15][16][17] . We developed 10 short-term WT cell lines from 8 patients (8 patient derived cell lines and 2 Six patient samples were obtained at time of diagnosis and two were obtained at time of recurrence (Aflac_2377T and CCLF_PEDS_0002_T).…”

Section: Wt Cell Lines Faithfully Recapitulate Genomic and Transcript...mentioning

confidence: 99%

Section: Wt Cell Lines Faithfully Recapitulate Genomic and Transcript...mentioning

confidence: 99%

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Targeting TRIP13 in Wilms Tumor with Nuclear Export Inhibitors

Mittal

Lee

Cooper

et al. 2022

Preprint

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Wilms tumor (WT) is the most common renal malignancy of childhood. Despite improvements in the overall survival, relapse occurs in ~15% of patients with favorable histology WT (FHWT). Half of these patients will succumb to their disease. Identifying novel targeted therapies in a systematic manner remains challenging in part due to the lack of faithful preclinical in vitro models. We established ten short-term patient-derived WT cell lines and characterized these models using low-coverage whole genome sequencing, whole exome sequencing and RNA-sequencing, which demonstrated that these ex-vivo models faithfully recapitulate WT biology. We then performed targeted RNAi and CRISPR-Cas9 loss-of-function screens and identified the nuclear export genes (XPO1 and KPNB1) as strong vulnerabilities. We observed that these models are sensitive to nuclear export inhibition using the FDA approved therapeutic agent, selinexor (KPT-330). Selinexor treatment of FHWT suppressed TRIP13 expression, which was required for survival. We further identified in vitro and in vivo synergy between selinexor and doxorubicin, a chemotherapy used in high risk FHWT. Taken together, we identified XPO1 inhibition with selinexor as a potential therapeutic option to treat FHWTs and in combination with doxorubicin, leads to durable remissions in vivo.

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“…We have isolated and described thirteen cell lines from patients with WT1 mutant Wilms tumors [33,34]…”

Section: Introductionmentioning

confidence: 99%

Gene expression studies of WT1 mutant Wilms tumor cell lines in the frame work of published kidney development data reveals their early stem cell origin

Royer‐Pokora

Wruck

Beier

2022

Preprint

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In order to get a better insight into the timing of WT1 mutant Wilms tumor development, we compared the gene expression profiles of nine established WT1 mutant Wilms tumor cell lines with published data from different kidney cell types during development. Publications describing genes expressed in nephrogenic precursor cells, ureteric bud cells, more mature nephrogenic epithelial cells and interstitial cell types were used. These studies uncovered that the WT1 mutant Wilms tumor cells lines express genes from the earliest nephrogenic progenitor cells, as well as from more differentiated nephron cells with the highest expression from the stromal/interstitial compartment. The expression of genes from all cell compartments points to an early developmental origin of the tumor in a common stem cell. Although variability of the expression of specific genes was evident between the cell lines the overall expression pattern was very similar. This is likely dependent on their different genetic backgrounds with distinct WT1 mutations and the absence/presence of mutant CTNNB1.

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Comprehensive Biology and Genetics Compendium of Wilms Tumor Cell Lines with Different WT1 Mutations

Cited by 14 publications

References 32 publications

Transcriptional fidelity enhances cancer cell line selection in pediatric cancers

Transcriptional fidelity enhances cancer cell line selection in pediatric cancers

Targeting TRIP13 in Wilms Tumor with Nuclear Export Inhibitors

Gene expression studies of WT1 mutant Wilms tumor cell lines in the frame work of published kidney development data reveals their early stem cell origin

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