Universität zu Köln

Royer-Pokora, Brigitte, Busch, Maike Anna, Tenbusch, Sarah, Schmidt, Mathias ORCID: 0000-0001-5554-9920, Beier, Manfred ORCID: 0000-0002-2482-1626, Woods, Andrew D., Thiele, Holger and Mora, Jaume (2021). Comprehensive Biology and Genetics Compendium of Wilms Tumor Cell Lines with Different WT1 Mutations. Cancers, 13 (1). BASEL: MDPI. ISSN 2072-6694

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Abstract

Simple Summary Wilms tumor is a childhood kidney tumor arising from embryonal cells. Wilms tumors are heterogeneous with several distinct subgroups that differ in their response to treatment. The genetic basis for these diverse forms of Wilms tumor is not fully understood. One subgroup of Wilms tumors is associated with mutations in the WT1 gene, encoding a transcription factor with a role in early kidney differentiation. Patients with WT1 mutant Wilms tumor may harbor germline mutations in this gene. Cell lines from Wilms tumors are notoriously difficult to establish and only few exist. We developed a method to cultivate cells from the WT1 mutant subtype of Wilms tumors and have established 11 cell lines with different mutations in WT1 to date. These cells will be instrumental to study the biology and genetics ultimately to develop precision treatments Purpose: WT1 mutant Wilms tumors represent a distinct subgroup, frequently associated with CTNNB1 mutations. The genetic basis for the development of this subtype is currently not fully understood. Methods: Live WT1 mutant Wilms tumors were collected during surgery of patients and cell cultures established in mesenchymal stem cell medium. They were studied for mutations in WT1 and CTNNB1, their differentiation capacity and protein activation status. Four cell lines were immortalized with a triple mutant ts SV40 largeT antigen and Telomerase. Results: 11 cell lines were established from Wilms tumors of nine patients, including a left and right tumor from the same patient and a primary and second tumor from another patient. Six patients had germ line and three were tumor specific mutations. All cell lines harbored only mutant or deleted WT1 genes. CTNNB1 was wild type in three, all others carried mutations affecting amino acid S45. They had variable and limited capacities for mesenchymal differentiation, a high migratory capacity and a low invasive potential. All cells showed an activation of multiple receptor tyrosine kinases and downstream signaling pathways. Conclusions: These cell lines represent an important new tool to study WT1 mutant Wilms tumors, potentially leading to new treatment approaches.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Royer-Pokora, Brigitte UNSPECIFIED UNSPECIFIED UNSPECIFIED Busch, Maike Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Tenbusch, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Mathias UNSPECIFIED orcid.org/0000-0001-5554-9920 UNSPECIFIED Beier, Manfred UNSPECIFIED orcid.org/0000-0002-2482-1626 UNSPECIFIED Woods, Andrew D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Mora, Jaume UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-584686
DOI:	10.3390/cancers13010060
Journal or Publication Title:	Cancers
Volume:	13
Number:	1
Date:	2021
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GROWTH-FACTOR RECEPTOR; MESENCHYMAL STEM-CELLS; TGF-BETA; CTNNB1 MUTATIONS; INVITRO GROWTH; IN-VITRO; PHYSIOLOGY; COMPONENT; CATENIN; MARKERS Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58468