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.
The detection of one nonsense point mutation and one missense WT1 gene point mutation adds to the accumulating evidence implicating this gene in a proportion of Wilms tumor patients.
A point mutation found in the WT1 gene in a sporadic Wilms' tumor without genitourinary abnormalities is identical with the most frequent point mutation in Denys-Drash syndrome.
Glypican 3 (GPC3), a membrane-bound heparin sulfate proteoglycan, is mutated in Simpson-Golabi-Behmel syndrome, characterized by tissue overgrowth and an increased risk of embryonal malignancies such as Wilms tumor.
The remaining four had chromosomal rearrangements: an unbalanced translocation, t(11;13), with a deletion including the WAGR (Wilms' tumor, aniridia, genitourinary abnormalities, and mental retardation) region, and three balanced rearrangements with what appear to be position effect breakpoints 3' of PAX6: (a) a t(7;11) with the 11p13 breakpoint approximately 30 kb downstream of PAX6, (b) a dir ins(12;11) with a breakpoint >50 kb from PAX6, and (c) an inv(11)(p13q13) with a breakpoint >75 kb downstream of PAX6.
We have now investigated whether mutations in the WT1 promoter could be associated with loss of control WT1 expression and subsequent Wilms tumour formation.
Desmoplastic small round cell tumors (DSRCTs) present a reciprocal chromosomal translocation, t(11;22)(p13;q12), that results in fusion of Ewing's sarcoma and Wilms' tumor (WT1) genes.
We report here that a patient with relapsed MDS after allo-BMT was successfully treated by the rapid discontinuation of immunosuppressive therapy at molecular relapse while monitoring Wilms tumor (WT1) gene expression levels.
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.
We present a vertical transmission of a nonsense mutation in exon 1 of the Wilms' tumorWT1 gene, from a mother who had Wilms' tumor in infancy and decreased fertility at adulthood, to her son who displayed genitourinary (GU) anomalies, gonadal dysgenesis with gonadoblastoma foci, and intra-abdominal Mullerian derivatives.
The Wilms' tumor (WT1) gene encodes a zinc finger transcription factor, which is preferentially expressed in acute leukemia cells and chronic myelogenous leukemia cells in blast crisis, but not in most normal cells.
Effective use of high-dose chemotherapy and autologous stem cell rescue for relapsed adult Wilms' tumor and a novel alteration in intron 1 of the WT1 gene.
They were examined because they had either isolated sporadic or familial aniridia, or aniridia with one or more of the WAGR (Wilms' tumour, aniridia, genital anomalies, and mental retardation) syndrome anomalies.
Although several genetic loci such as the WT1 gene have been known to relate to the biology of WT, the cause of the tumor is complex and the implicated molecular pathways are largely unknown.
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.
We describe here a novel WT1 gene mutation, i.e. a point mutation at intron 7 (+2) in both the tumor and the germline cells of a patient with Wilms' tumor and congenital male genitourinary malformation, but without renal disorder.