Wilms Tumor

Epidemiology
Worldwide : 1 child per 10,000 younger
than 15 years
USA:
• 6% of childhood cancers
Wilms • Total incidence : 450-500 cases /year.
Tumor
Slightly elevated for blacks (both
American and African
NWTS : median age at onset is 38
months
A small percentage  hereditary :
autosomal dominant
 Maternal hormone exposure
during pregnancy

↑ risk of
Wilms Tumor

Paternal Occupation Genetic Predisposition

Wilms' tumor shows association with congenital
anomalies:
• WAGR syndrome (Wilms' tumor, aniridia,
genitourinary malformations, and mental
retardation)
• Beckwith-Wiedemann syndrome (an overgrowth
syndrome : exomphalos, visceromegaly,
macroglossia, and hyperinsulinemic hypoglycemia)
• Hemihypertrophy
• Urologic anomalies, such as lobular nephromegaly,
hypospadias, and cryptorchidism
 Molecular Biology and Genetics

The development of Wilms' tumor  involve changes

in a number of genes that control normal kidney
development and growth

The biologic pathways  involve several genetic loci:

• two genes on chromosome 11p (the Wilms‘
tumor suppressor gene WT1)
• chromosome 11p15 (the putative Wilms' tumor
suppressor gene WT2)
• Loci at 1p, 7p, 16q, and 17p (the p53 tumor
suppressor gene)
 WT1

• WT1 has important functions during genitourinary

development, highly restricted temporal and spatial
expression in glomerular precursors and by the
failure of kidney development in WT1-null mice.
• WT1 is mutated in approximately 20% of all patients
with Wilms' tumors.
• 90% of patients with the even rarer Denys- Drash
syndrome harbor germline mutations in WT1.
 WT2

• Karyotypes of Wilms‘ tumors have demonstrated

DNA loss at the llp15 locus.
• Several genes (IGF2, p577KIP2, H19, KVL.QT1) that
regulate somatic growth are subject to dysregulated
imprinting, including the gene for Beckwith-
Wiedeman syndrome (BWS).
• This is the location for the putative second Wilms'
tumor gene, WT2, which has yet to be cloned.
• Insulin-like growth factor 2 (IGF2), which resides at
llp15, as the candidate WT2 gene because it is
subjected to genomic imprinting.
• Investigators in Japan identified a paternally
expressed imprinted gene, PEG8/IGF2AS, in this
locus.
• PEG8/IGF2AS and IGF2 were found to be
overexpressed in Wilms' tumor samples, at levels 10
to 100 times greater than in normal kidney  may
be a marker for Wilms' tumor