In addition, the analysis of the expression of other 11p15 imprinted genes and kidney-developmentally regulated genes indicates that IGF2 overexpression, inappropriate coexpression of RET and GDNF and, in some cases, down-regulation of CDKN1C may also play an important role in the pathogenesis of WT.
Two other 11p15.5 loci, the linked and oppositely imprinted H19 and IGF2 genes, have been previously implicated in WT pathogenesis, and several of the tumors with persistent KIP2 mRNA expression and absence of KIP2 coding mutations showed full inactivation of H19.
Our previous work with somatic cell hybrids mapped a tumor suppressor gene for the G401 Wilms' tumor cell line to a approximately 500-kb region of 11p15.5 that includes p57.
Our data indicate that if the p57KIP2 gene is imprinted in humans and expressed exclusively from the maternal allele, reactivation of the paternal allele has occurred in all five Wilms' tumor samples analyzed in this study.
We also examined p57KIP2 expression in the normal kidney and tongue of patients with Beckwith-Wiedemann syndrome (BWS), which predisposes to WT and also involves LOI of IGF2 and H19.