We investigated pain sensitivity in humans with WAGR (Wilms tumor, aniridia, genitourinary anomaly, and range of intellectual disabilities) syndrome, who have variably sized heterozygous deletion of the 11p13 region.
Our previous study of congenital aniridia patients revealed a noticeable number of aniridia patients with WAGR-region deletions but without Wilms' tumor in their medical history.
In the present study, combination vaccine of Wilms' tumor gene 1(WT1) protein-derived CTL and helper peptides induced the strong infiltration of WT1-specific CD8<sup>+</sup> T cells into mouse tumor at frequencies of 8.8%, resulting in the formation of multiple microscopic necrotic lesions in the tumor, whereas the frequencies of WT1-specific CD8<sup>+</sup> T cell infiltration into the tumor in the vaccination of the CTL peptide alone were only 0.32%.
All described patients presented with similar neuroimaging features including thin corpus callosum, mild to moderate cerebellar atrophy and diffuse periventricular and profound hypomyelinating leukodystrophy involving supratentorial white matter with classical compromise linked to inherited non-somatic WT1 gene mutations in a similar pattern to Denys-Drash syndrome, including nephrotic syndrome with different glomerular disease, chronic renal failure, intersex disorder with ambiguous genitalia, and early occurrence of specific tumors, such as Wilms' tumor and gonadoblastoma.
These 5 animals presented tumors with histology and cells highly staining positive for PCNA and Wilms' tumor protein antibody characteristics of Wilms' tumor.
The identification of human Wilms' tumor gene 1 (WT1) protein-derived cytotoxic T lymphocyte (CTL) epitopes and the in vivo efficacy of WT1 peptide-based immunotherapy in a mouse model were reported in 2000.
Interstitial deletions of the 11p13 region are known to cause WAGR (Wilms tumor, aniridia, genitourinary malformation, and "mental retardation") syndrome, a contiguous gene deletion syndrome due to haploinsufficiencies of the genes in this region, including WT1 and PAX6.
An amplified exon 9 sequence of the WT1 gene showing similarity with exon 9 of TV-A, F and exon 10 of TV-B, D and E with a deletion of single nucleotide 'A' causing frame shift in the 4th zinc finger domain of the WT1 protein resulted in Wilms' tumor condition.
Mutations in WT1 are observed in 20% of Wilms tumors (a pediatric kidney cancer), but the in vivo WT1 targets and associated molecular pathways involved in the etiology of Wilms tumor are still elusive.
Although the WT1 gene, located at 11p13, has been proven to be implicated in the development of Wilms tumor, other genes such as MYCN are also involved.
The lack of Wilms tumor or other related phenotypes suggests the expansion of WT1 gene analysis in patients with focal segmental glomerulosclerosis, regardless of age or presence of typical Denys-Drash or Frasier syndrome clinical features.
Wilms' tumor gene 1 (WT1) gene expression was analyzed in 32 patient with acute myeloid leukemia (AML) and 18 with acute lymphoblastic leukemia (ALL) to investigate whether it could serve as a MRD marker.
We demonstrate abundant PAX3 and absence of PAX2 expression in a novel cell line (WitP3) isolated from the stromal portion of a WT bearing a homozygous deletion of the WT1 gene.
Although the majority of congenital urogenital abnormalities are not due to constitutional defects of the WT1 gene, our findings provide a rational for considering WT1 mutational analysis as one of the screening options in newborns with congenital defects of the urogenital tract due to the associated high risk of WT.
Knockdown of WT1 protein by siRNA significantly increased the cellular renin mRNA content, while overexpression of WT1(-KTS) reduced renin gene expression in stable and transiently transfected cells.