SNP Shot: Genomic Insights

Wilms tumor is a type of kidney cancer that mainly affects children. It's almost always diagnosed before age 10, and in about two-thirds of cases, it's found before the child turns 5.

Often, the first sign of Wilms tumor is swelling in the abdomen or a lump in the kidney that can be felt during an exam. Some children with Wilms tumor may also experience abdominal pain, fever, a low red blood cell count (anemia), blood in their urine (hematuria), or high blood pressure (hypertension). Other symptoms can include loss of appetite, weight loss, feeling sick to their stomach (nausea), vomiting, and feeling very tired (lethargy).

Wilms tumor can occur in either one or both kidneys. In about 5 to 10 percent of those affected, multiple tumors develop in one or both kidneys. The cancer can spread (metastasize) from the kidneys to other areas of the body. In rare instances, Wilms tumor develops outside the kidneys, such as in the genital tract, bladder, abdomen, chest, or lower back. The reason for this is not well understood.

With appropriate treatment, the survival rate for children with Wilms tumor is 90 percent. However, there is a risk the cancer will return (recur), which varies from 15 to 50 percent, depending on the characteristics of the original tumor. Recurrences typically happen within the first two years after treatment, either in the kidneys or in other tissues like the lungs. People who have had Wilms tumor may face related health issues or long-term effects from their treatment as adults, including reduced kidney function, heart problems, and the development of other cancers.

Inheritance:

In most cases, Wilms tumor isn't caused by inherited genetic factors and doesn't run in families. About 90 percent of these cancers result from changes in genes (somatic variants) that occur during a person's lifetime and are found only in the tumor cells. The remaining 10 percent of Wilms tumor cases are caused by genetic changes present in all the body's cells (germline variants). These variants can lead to Wilms tumor alone, without other symptoms, or to syndromes where Wilms tumor is just one of several features. These cases follow an autosomal dominant inheritance pattern, meaning that having one copy of the changed gene in each cell is enough to cause a Wilms tumor-related syndrome or increase the risk of developing the cancer on its own. Most of these cases are due to new (de novo) variants that occur during the creation of reproductive cells (eggs or sperm) or early in the development of the embryo. The AMER1 gene is located on the X chromosome (one of the sex chromosomes). When Wilms tumor is caused by changes in this gene, it follows an X-linked dominant pattern. In individuals with two X chromosomes (typically females), a change in one of the two copies of the gene in each cell is enough to increase the risk of developing the cancer. In individuals with only one X chromosome (typically males), a change in the single copy of the gene in each cell increases their risk. In many instances, the underlying genetic cause of Wilms tumor and its inheritance pattern remain unclear.