Homozygous somatic Wt1 point mutations in sporadic unilateral Wilms tumor.
Wilms tumor may be caused by loss of function of genes at different loci. A Wilms tumor suppressor gene, WT1, at chromosome 11 band p13, has recently been cloned and characterized. WT1 has been implicated in the development of Wilms tumor by virtue of mutations in patients with genitourinary anomalies and susceptibility to Wilms tumor. Homozygous intragenic mutations have been reported in Wilms tumors, but usually not in sporadic unilateral Wilms tumors, which constitute the majority of Wilms tumor cases. Using the single-strand conformational polymorphism assay, we have identified three sporadic unilateral Wilms tumors with homozygous point mutations: one with a de novo germ-line nonsense point mutation within WT1 exon 8, and two carrying a somatic mutation within WT1 exon 10. In all three cases loss of the wild-type allele was demonstrated by tumor loss of heterozygosity. This report provides an example of two somatic mutations in the same tumor expected to inactivate WT1 function.
Department of Cancer Biology, Cleveland Clinic Foundation, OH 44195.
M J
MJ
Coppes
G J
GJ
Liefers
P
P
Paul
H
H
Yeger
B R
BR
Williams
D000595:Amino Acid Sequence; D001483:Base Sequence; D002871:Chromosome Banding; D002880:Chromosomes, Human, Pair 11; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D016147:Genes, Tumor Suppressor; D006720:Homozygote; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D009396:Wilms Tumor / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense