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How Wilms tumors form

A Wilms tumor can form when early kidney cells don’t mature and instead grow out of control.

The kidneys develop very early as a fetus grows in the womb. Sometimes, certain cells that are programmed to turn into kidney cells don’t mature like they’re supposed to. Instead, they stay in the body in the form of early (not mature) kidney cells. They might stay in the body even after the baby is born.

Usually, these cells mature by the time a child is 3 to 4 years old. But if this doesn’t happen, the cells might somehow begin to grow out of control. This can result in a Wilms tumor.

How gene changes can affect kidney development

Cells are the building blocks for all life, including the human body. Our genes control how our cells work.

Different genes have different functions in our bodies. If they are working properly, certain genes help control when our cells grow, divide to make new cells, or repair mistakes in our DNA (the chemical in each of our cells that makes up our genes).

Genes also cause cells to die when they’re supposed to. If these genes aren’t working properly, it can lead to cells growing out of control.

For example:

• Changes in genes that normally help cells grow, divide, or stay alive can lead to these genes being more active than they should be, causing them to become oncogenes. These genes can result in cells growing out of control.
• Genes that normally help keep cell division under control or cause cells to die at the right time are known as tumor suppressor genes. Changes that turn off these genes can result in cells growing out of control.
• Some genes normally help repair mistakes in a cell’s DNA. Changes that turn off these DNA repair genes can result in the buildup of DNA changes within a cell, which might lead to them growing out of control.

Any of these types of DNA changes might lead to cells growing out of control and forming a tumor. To learn more, see .

Gene changes in Wilms tumors

Changes in certain genes in early kidney cells can lead to problems as the kidneys develop.

Sometimes these gene changes are passed on from a parent to a child (inherited). But most Wilms tumors don’t seem to be caused by inherited gene mutations. Instead, they seem to be caused by gene changes that happen early in a child’s life, perhaps even before birth.

Doctors have found that some Wilms tumors have changes in specific genes.

In a small number of Wilms tumors, the cells have changes in (or loss of) the WT1 gene. The WT1 gene is a tumor suppressor gene on chromosome 11. Changes in this gene and some other genes on chromosome 11 can lead to overgrowth of certain body tissues. This may explain why some other growth abnormalities, like those described in Risk Factors for Wilms Tumors, are sometimes found along with Wilms tumors.

Other genes that are sometimes altered in Wilms tumor cells include CTNNB1, AMER1 (WTX), IGF2, DROSHA, and TP53.

Several other gene or chromosome changes have been found in some Wilms tumor cells. Typically, more than one gene change is needed to cause cancer. None of the gene changes found so far are seen in all Wilms tumors. There are also likely to be other gene changes that have not yet been found.

Researchers now understand some of the gene changes that can occur in Wilms tumors, but it’s still not clear what causes these changes. Some gene changes can be inherited from a parent, but most Wilms tumors are not the result of known inherited syndromes.

Some gene changes may just be random events that sometimes happen inside a cell, without having an outside cause. There are no known lifestyle-related or environmental causes of Wilms tumors, so it's important to know that there is nothing these children or their parents could have done to lower the risk of these cancers.