WT1 Tumor Suppressor Gene: A
Constitutional Deletion
Chromosome 11p13
WAGR Syndrome
Nonhereditary Wilms Tumor (33%)
10 Exons Encoding for
a 45-49 kd Protein
Homology to Early Growth Response 1 (EGR1)
Sequence
Specific DNA Binding
Regulate
Transcription of Other Genes
30 to 40% of
Wilms with Loss of Heterozygosity for region with WT1
WT1 Role
Gonadal Development
WAGR Syndrome
Denys-Drash Syndrome
Dominant Negative
Mechanism
Abnormal Product
inhibits Normal Product
WT2: Tumor Suppressor Gene
Chromosome 11p15.5
Linkage Analysis
Associated with Beckwith-Weidemann Syndrome
Tumors with Loss of
Heterozygosity
Maternal Copy is Lost
Genomic Imprinting (One alleles marked in a
parental-specific
manner as inactive)
Candidates for WT2
Insulin-Like Growth
Factor Type II (IGF-2 on 11p14.1)
Embryonal Growth Factor in Wilms Tumors
Paternal Allele Only Expressed
H19: Maternal Allele
Only Expressed
WT 3: 16q Tumor-Specific Loss of
Heterozygosity
Associated with Poor
Prognosis
Involved with Tumor
Progression
1p Tumor-Specific Loss of
Heterozygosity
Trisomy 18
