Combined mutation of Vhl and Trp53 causes renal cysts and tumours in mice
Abstract: The combinations of genetic alterations that cooperate with von Hippel–Lindau (VHL) mutation to cause clear cell renal cell carcinoma (ccRCC) remain poorly understood. We show that the TP53 tumour suppressor gene is mutated in approximately 9% of human ccRCCs. Combined deletion of Vhl and Trp53 in primary mouse embryo fibroblasts causes proliferative dysregulation and high rates of aneuploidy. Deletion of these genes in the epithelium of the kidney induces the formation of simple cysts, atypical cysts and neoplasms, and deletion in the epithelia of the genital urinary tract leads to dysplasia and tumour formation. Kidney cysts display a reduced frequency of primary cilia and atypical cysts and neoplasms exhibit a pro‐proliferative signature including activation of mTORC1 and high expression of Myc, mimicking several cellular and molecular alterations seen in human ccRCC and its precursor lesions. As the majority of ccRCC is associated with functional inactivation of VHL, our findings suggest that for a subset of ccRCC, loss of p53 function represents a critical event in tumour development.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Combined mutation of Vhl and Trp53 causes renal cysts and tumours in mice ; volume:5 ; number:6 ; year:2013 ; pages:949-964 ; extent:16
EMBO molecular medicine / European Molecular Biology Organization ; 5, Heft 6 (2013), 949-964 (gesamt 16)
- Creator
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Albers, Joachim
Rajski, Michal
Schönenberger, Désirée
Harlander, Sabine
Schraml, Peter
von Teichman, Adriana
Georgiev, Strahil
Wild, Peter J.
Moch, Holger
Krek, Wilhelm
Frew, Ian J.
- DOI
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10.1002/emmm.201202231
- URN
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urn:nbn:de:101:1-2023020306565112085453
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:23 AM CEST
Data provider
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Associated
- Albers, Joachim
- Rajski, Michal
- Schönenberger, Désirée
- Harlander, Sabine
- Schraml, Peter
- von Teichman, Adriana
- Georgiev, Strahil
- Wild, Peter J.
- Moch, Holger
- Krek, Wilhelm
- Frew, Ian J.
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8q24 clear cell renal cell carcinoma germline variant is associated with VHL mutation status and clinical aggressiveness
VHL mutation as a cause of three generations familial pheochromocytoma
The VHL-dependent regulation of microRNAs in renal cancer
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Are lung cysts in renal cell cancer (RCC) patients an indication for FLCN mutation analysis?
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VHL mutation-mediated SALL4 overexpression promotes tumorigenesis and vascularization of clear cell renal cell carcinoma via Akt/GSK-3β signaling
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Interaktion der VHL- und TSC1-Mutation in der molekularen Pathogenese des klarzelligen Nierenzellkarzinoms
Renal Tubular HIF-2α Expression Requires VHL Inactivation and Causes Fibrosis and Cysts
CpG methylation profiling in VHL related and VHL unrelated renal cell carcinoma
A multinodular goiter as the initial presentation of a renal cell carcinoma harbouring a novel VHL mutation
8q24 clear cell renal cell carcinoma germline variant is associated with VHL mutation status and clinical aggressiveness
VHL mutation as a cause of three generations familial pheochromocytoma
The VHL-dependent regulation of microRNAs in renal cancer
Identifizierung der somatischen VHL-Hypermethylierung und Bedeutung der somatischen VHL-Mutationen für die unterschiedlichen histopathologischen Subtypen der sporadischen Nierenzellkarzinome
Are lung cysts in renal cell cancer (RCC) patients an indication for FLCN mutation analysis?
Crizotinib-Associated Renal Cysts: A Case Series
VHL mutation-mediated SALL4 overexpression promotes tumorigenesis and vascularization of clear cell renal cell carcinoma via Akt/GSK-3β signaling
Evaluation of Bosniak category IIF complex renal cysts
Interaktion der VHL- und TSC1-Mutation in der molekularen Pathogenese des klarzelligen Nierenzellkarzinoms
Renal Tubular HIF-2α Expression Requires VHL Inactivation and Causes Fibrosis and Cysts
CpG methylation profiling in VHL related and VHL unrelated renal cell carcinoma
A multinodular goiter as the initial presentation of a renal cell carcinoma harbouring a novel VHL mutation
8q24 clear cell renal cell carcinoma germline variant is associated with VHL mutation status and clinical aggressiveness
VHL mutation as a cause of three generations familial pheochromocytoma
The VHL-dependent regulation of microRNAs in renal cancer
Identifizierung der somatischen VHL-Hypermethylierung und Bedeutung der somatischen VHL-Mutationen für die unterschiedlichen histopathologischen Subtypen der sporadischen Nierenzellkarzinome
Are lung cysts in renal cell cancer (RCC) patients an indication for FLCN mutation analysis?
Crizotinib-Associated Renal Cysts: A Case Series
VHL mutation-mediated SALL4 overexpression promotes tumorigenesis and vascularization of clear cell renal cell carcinoma via Akt/GSK-3β signaling
Evaluation of Bosniak category IIF complex renal cysts