WT1

About WT1

WT1 on chromosome 11p13 encodes a zinc finger transcription factor, existing in multiple isoforms, that is essential for the development of the kidneys and gonads, as well as the heart, spleen, and other mesothelial tissues. The gene was identified in 1990 as a tumor suppressor for Wilms tumor, the most common kidney cancer of childhood. Germline WT1 alterations cause several syndromes. WAGR syndrome, combining Wilms tumor, aniridia, genitourinary anomalies, and intellectual disability, results from deletions spanning WT1 and the neighboring PAX6 gene. Denys Drash syndrome, usually caused by missense variants in the zinc finger domain, combines early onset kidney disease due to diffuse mesangial sclerosis, disorders of sex development, and a high risk of Wilms tumor. Frasier syndrome, caused by splice site variants that alter the balance of WT1 isoforms, combines focal segmental glomerulosclerosis with gonadal dysgenesis and a risk of gonadoblastoma. WT1 mutations occur in a minority of sporadic Wilms tumors, which more often involve other genes such as CTNNB1 and WTX. In acute myeloid leukemia, WT1 is often overexpressed and sometimes mutated, and its expression has been used as a marker for monitoring residual disease. WT1 is also a target of cancer vaccine research.