Wilms' tumor

Wilms (/vɪlmz/) tumor, Wilms' tumor, or nephroblastoma is a cancer of the kidneys that typically occurs in children, rarely in adults. It is named after Dr. Max Wilms, the German surgeon (1867–1918) who first described it.

Approximately 500 cases are diagnosed in the U.S. annually. The majority (75%) occur in otherwise normal children; a minority (25%) are associated with other developmental abnormalities. It is highly responsive to treatment, with about 90% of patients surviving at least five years.

Signs and symptoms

Typical signs and symptoms of Wilms' tumor include the following:

Pathogenesis

Most nephroblastomas are on one side of the body only and are found on both sides in less than 5% of cases, although patients with Denys-Drash syndrome mostly have bilateral or multiple tumors. They tend to be encapsulated and vascularized tumors that do not cross the midline of the abdomen. In cases of metastasis it is usually to the lung. A rupture of Wilms tumor puts the patient at risk of bleeding and peritoneal dissemination of the tumor. In such cases, surgical intervention by a surgeon who is experienced in the removal of such a fragile tumor is imperative.

WT1

Wilms tumor protein is a protein that in humans is encoded by the WT1 gene on chromosome 11p.

Function

This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-rich DNA-binding domain at the N-terminus. It has an essential role in the normal development of the urogenital system, and it is mutated in a subset of patients with Wilms' tumor, the gene's namesake. Multiple transcript variants, resulting from alternative splicing at two coding exons, have been well characterized. There is also evidence for the use of non-AUG (CUG) translation initiation site upstream of, and in-frame with the first AUG, leading to additional isoforms.

Structure

The WT1 gene product shows similarity to the zinc fingers of the mammalian growth regulated early growth response protein 1 (EGR1) and (EGR2) proteins.

Clinical significance

Wilm's tumour tumor suppressor gene1 (WT1) causes an embryonic malignancy of the kidney, affecting around 1 in 10,000 infants. It occurs in both sporadic and hereditary forms. Inactivation of WT1 causes Wilm's tumour, and Denys-Drash syndrome (DDS), leading to nephropathy and genital abnormalities. The WT1 protein has been found to bind a host of cellular factors, e.g. p53, a known tumor suppressor.