Transcriptomics,Genomics

Dataset Information

39

Chemotherapy induced terminal muscle differentiation in WT1 mutant Wilms tumors is associated with cell cycle exit and a loss of growth potential


ABSTRACT: Patients with Wilms tumors are efficiently treated by chemotherapy; however, tumors with mutant WT1 genes show a poor volume response. Here we used an unbiased gene expression profiling approach and identified a novel mechanism of conventional chemotherapy that explains how the cure of these patients is brought about. Transcription profiling of an untreated WT1 mutant Wilms tumor (Wilms10) and a corresponding lung metastasis that was detected after long-term chemotherapy, revealed the induction of a myogenic transcriptional network with concomitant down-regulation of cell cycle genes. Cell culture experiments showed convincingly that the Wilms10 tumor cells from this lung metastasis had lost their growth potential due to an induction of terminal skeletal muscle differentiation by chemotherapy. These results were confirmed using a set of Wilms tumors with mutant WT1 genes that were treated by preoperative chemotherapy. We conclude here that chemotherapy-induced terminal skeletal muscle differentiation of Wilms tumors with concomitant loss of growth potential enables the cure of Wilms tumor patients with WT1 mutations in the clinical setting. We have shown before that cell lines derived from Wilms tumors with WT1 mutations have characteristic features of mesenchymal stem cells and it will be of great interest to evaluate whether other tumor types with stem cell features show a differentiation reponse to chemotherapy. Overall design: Array expression experiment of direct Wilms tumor and lung metastasis tissue

INSTRUMENT(S): Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version)

SUBMITTER: Brigitte Royer-Pokora  

PROVIDER: GSE63616 | GEO | 2018-06-17

REPOSITORIES: GEO

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Publications

Chemotherapy and terminal skeletal muscle differentiation in WT1-mutant Wilms tumors.

Royer-Pokora Brigitte B   Beier Manfred M   Brandt Artur A   Duhme Constanze C   Busch Maike M   de Torres Carmen C   Royer Hans-Dieter HD   Mora Jaume J  

Cancer medicine 20180315 4


Wilms tumors (WT) with WT1 mutations do not respond well to preoperative chemotherapy by volume reduction, suggesting resistance to chemotherapy. The histologic pattern of this tumor subtype indicates an intrinsic mesenchymal differentiation potential. Currently, it is unknown whether cytotoxic treatments can induce a terminal differentiation state as a direct comparison of untreated and chemotherapy-treated tumor samples has not been reported so far. We conducted gene expression profiling of 11  ...[more]

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