|Transcript ID (GRCh37/hg19)||ENST00000332351|
|Tumor Type||Primary Site|
This gene is a known cancer gene.
WT1 encodes for a transcription factor containing an N-terminal transactivation domain and a C-terminal zinc-finger domain necessary for the development of the urogenital system. The precise roles of WT1 in normal and malignant hematopoiesis remain uncertain. New emerging supports a novel role of WT1 in the regulation of epigenetic programs through its interaction with TET proteins in the 5=hydroxymethylation of cytosines. WT1 mutations are found in 6% of acute myeloid leukemia overall, and about 8-13% in cytogenetically normal AML. Higher frequencies are present in biallelic CEBPA mutated acute myeloid leukemia (14%), followed by t(15;17)/PML-RARA (11.0%), and FLT3-ITD (8.5%,). WT1 mutations are associated with younger age in AML. WT1 mutations are typically putative loss of function mutations and most frequently occur in exon 7 or exon 9. About 75% of these mutations are frameshift, and the remaining are missense, nonsense, splice site or inframe indel mutations. In some cases two or more mutations in WT1 may occur. In addition, WT1 mutations may coexist with mutations in NPM1, FLT3, among others. WT1 is overexpressed in the majority of AML, giving rise to the concept that it may act as both a tumor suppressor and oncogene, depending on the context. Several studies showed that WT1 mutations are associated with a worse prognosis in cytogenetically normal acute myeloid leukemia, although one study including patients from three German-Austrian AML study protocols demonstrated no association with overall survival or relapse-free survival. Given its over-expression in AML, clinical trials employing peptide vaccination strategy against WT1 has been ongoing in AML patients.