Mutations in WTX are found in Wilms tumor, a form of pediatric kidney cancer and in patients suffering from OSCS (Osteopathia striata with cranial sclerosis), a sclerosing bone disorder.
WTX encodes a tumor suppressor implicated in the pediatric kidney cancer Wilms tumor and in mesenchymal differentiation with potentially distinct functions in the cytoplasm, at the plasma membrane, and in the nucleus.
The adenomatous polyposis coli (APC) membrane recruitment (Amer) family proteins Amer1/Wilms tumour gene on the X chromosome and Amer2 are binding partners of the APC tumour suppressor protein, and act as negative regulators in the Wnt signalling cascade.
WTX is a tumor suppressor gene expressed during embryonic development and inactivated in 20-30% of cases of Wilms tumor, the most common pediatric kidney cancer.
This has been illustrated by the findings that mutations of Wnt/β-catenin pathway-related WT1, β-catenin, and WTX together account for about one-third of Wilms tumor cases.
The 17.94 cell line contained a TP53 mutation, consistent with the anaplastic histology of the original tumor, but lacked mutations in WT1, WTX, or CTNNB1, which are the other genes involved in WT pathogenesis.
We found that abnormalities of WTX and CTNNB1 were mutually exclusive, and that although CTNNB1 mutation was frequent in WTs with WT1 abnormality, but rare in WTs without, the incidences of WTX abnormality were similar between WTs with or without WT1 abnormality.
Genes identified as being mutated in Wilms' tumour include TP53, a classic tumour suppressor gene (TSG); CTNNB1 (encoding β-catenin), a classic oncogene; WTX, which accumulating data indicate is a TSG; and WT1, which is inactivated in some Wilms' tumours, similar to a TSG.
Wilms' tumor (WT), the most common pediatric renal malignancy, is associated with mutations in several well-characterized genes, most notably WT1, CTNNB1, WTX, and TP53.
Therefore 8 SNPs-distributed over the whole length of the WTX gene-were investigated by high resolution melting curve analysis (HRMA) and sequencing of genomic DNA from nephroblastoma patients (NB) and controls.
The recent description of a new X chromosome tumor suppressor gene, WTX, that is commonly inactivated in Wilms' tumor prompted us to examine the possible involvement of WTX in a case of Wilms' tumor containing an apparently balanced reciprocal translocation between chromosomes X and 18 (t(X;18)(q11;p11)).