title: Constitutional and somatic mutations in the WT1 gene in Wilms' tumor patients.
abstract: Wilms' tumor development, like most tumors, involves multiple genetic alterations affecting diverse genes. Only one of these has thus far been identified, the Wilms' tumor 1 (WT1) gene on 11p13, which functions as a tumor suppressor gene. We assessed the involvement of the WT1 gene constitutionally and somatically in 26 Wilms' tumor patients. Of these, the clinical data suggest a constitutional pre-disposition in 12 bilateral cases and 7 cases with early onset. We employed Southern blot analysis and PCR-based markers for analyses of somatic allelic losses in chromosome bands 11p13, 11p15 and 16q and screened for point mutations in exons 2-10 of the WT1 gene with denaturing gradient gel electrophoresis (DGGE). Of the 12 cases with multiple tumors, 1 exhibited a constitutional 11p13 deletion and a somatic stop mutation in exon 4 of the WT1 gene and 2 harbored constitutional mutations in the WT1 gene: a pre-mature stop codon in exon 6 in a boy with bilateral cryptorchidism and bilateral Wilms' tumors and an intragenic deletion in a girl with bilateral WT. Three additional bilateral tumors displayed WT1 rearrangements or allelic losses with 11p13 markers. Four of 7 patients with an early onset of unilateral tumor had losses of 11p13, though no WT1 mutations were detected. Two of the remaining cases that did not show any somatic or constitutional 11p13 alterations had Beckwith-Wiedemann syndrome, known to involve the 11p15 region.
authors.affiliation: Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Nordenskjöld
authors.forename: E
authors.initials: E
authors.lastname: Friedman
authors.forename: B
authors.initials: B
authors.lastname: Sandstedt
authors.forename: S
authors.initials: S
authors.lastname: Söderhäll
authors.forename: M
authors.initials: M
authors.lastname: Anvret
mesh_terms: D000483:Alleles; D001483:Base Sequence; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics; D004276:DNA, Satellite / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004586:Electrophoresis / Q000379:methods; D005091:Exons; D005260:Female; D017353:Gene Deletion; D015321:Gene Rearrangement; D016162:Genes, Wilms Tumor / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D025721:WT1 Proteins; D009396:Wilms Tumor / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D004276:DNA, Satellite; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D025721:WT1 Proteins