TY  - JOUR
A1  - Poulat, F.
A1  - Morin, D.
A1  - Konig, A.
A1  - Brun, P.
A1  - Giltay, J.
A1  - Sultan, C.
A1  - Dumas, R.
A1  - Gessler, Manfred
A1  - Berta, P.
T1  - Distinct molecular origins for Denys-Drash and Frasier syndromes
N2  - The direct involvment of the Wilm's tumor suppressor gene (WTl) in Denys-Drash syndrome through mutations within exons 8 or 9 has recently been established. The absence of such alterations in three patients with Frasier syndrome provides a molecular basis for distinguishing these two syndromes that are associated with streak gonads, pseudohermaphroditism and renal failure.
KW  - Biochemie
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59172
ER  - 
TY  - JOUR
A1  - Gessler, Manfred
A1  - König, A.
A1  - Bruns, G. A. P.
T1  - The genomic organization and expression of the WT1 gene
N2  - The Wilms tumor gene WTl, a proposed tumor suppressor gene, has been identifled based on its location within a homozygous deletion found in tumor tissue. The gene encodes a putative transcription factor containing a Cys/His zinc finger domain. The critical homozygous deletions, however, are rarely seen, suggesting that in many cases the gene may be inactivated by more subtle alterations. To facilitate the seareh for smaller deletions and point mutations we have established the genomic organization of the WTl gene and have determined the sequence of all 10 exons and flanking intron DNA. The pattern of alternative splicing in two regions has been characterized in detail. These results will form the basis for future studies of mutant alleles at this locus.
KW  - Biochemie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59195
ER  - 
TY  - JOUR
A1  - Gessler, Manfred
A1  - König, A.
A1  - Arden, K.
A1  - Grundy, P.
A1  - Orkin, S. H.
A1  - Sallan, S.
A1  - Peters, C.
A1  - Ruyle, S.
A1  - Mandell, J.
A1  - Li, F.
A1  - Cavenee, W.
A1  - Bruns, G. A.
T1  - Infrequent mutation of the WT1 gene in 77 Wilms' Tumors
N2  - Homozygous deletions in Wilms' tumor DNA have been a key step in the identification and isolation of the WTI gene. Several additional loci are also postulated to contribute to Wilms' tumor formation. To assess the frequency of WTI alterations we have analyzed the WTI locus in a panel of 77 Wilms' tumors. Eight tumors showed evidence for large deletions of several hundred or thousand kilobasepairs of DNA, some of which were also cytogenetically detected. Additional intragenic mutations were detected using more sensitive SSCP analyses to scan all 10 WTI exons. Most of these result in premature stop codons or missense mutations that inactivate the remaining WTI allele. The overall frequency of WTI alterations detected with these methods is less than 15%. While some mutations may not be detectable with the methods employed, our results suggest that direct alterations of the WTI gene are present in only a small fraction of Wilms' tumors. Thus, mutations at other Wilms' tumor loci or disturbance of interactions between these genes likely play an important role in Wilms' tumor development.
KW  - Wilms' tumor
KW  - WTI
KW  - Zinc finger gene
KW  - Tumor suppressor gene
KW  - Nephroblastoma
KW  - Deletion analysis
KW  - SSCP analysis
KW  - Mutation screening
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-34308
ER  -