Homozygous inactivation of WT1 in a Wilms' tumor associated with the WAGR syndrome.
Wilms' tumor is a childhood nephroblastoma that is postulated to arise through the inactivation of a tumor suppressor gene by a two-hit mechanism. A candidate 11p13 Wilms' tumor gene, WT1, has been cloned and shown to encode a zinc finger protein. Patients with the WAGR syndrome (Wilm's tumor, aniridia, genitourinary abnormalities, and mental retardation) have a high risk of developing Wilms' tumor and they carry constitutional deletions of one chromosome 11 allele encompassing the WT1 gene. Analysis of the remaining WT1 allele in a Wilms' tumor from a WAGR patient revealed the deletion of a single nucleotide in exon 7. This mutation likely played a key role in tumor formation, as it prevents translation of the DNA-binding zinc finger domain that is essential for the function of the WT1 polypeptide as a transcriptional regulator.
Gessler
M
M
Institut für Humangenetik, Philipps-Universität Marburg, Germany.
König
A
A
Moore
J
J
Qualman
S
S
Arden
K
K
Cavenee
W
W
Bruns
G
G
D000293:Adolescent; D000483:Alleles; D000595:Amino Acid Sequence; D015783:Aniridia / Q000235:genetics; D001483:Base Sequence; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11; D003456:Cryptorchidism / Q000235:genetics; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D013577:Syndrome; D009396:Wilms Tumor / Q000235:genetics*