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Although there is a clear link between Wilms tumors and certain birth defect syndromes and genetic changes, most children with this type of cancer do not have any known birth defects or inherited gene changes.

Researchers do not yet know exactly why some children get Wilms tumors, but they have made great progress in understanding how normal kidneys develop, as well as how this process can go wrong, leading to a Wilms tumor.

The kidneys develop very early as a fetus grows in the womb. Some of the cells that are supposed to develop into mature kidney cells sometimes stay as early kidney cells instead, and might remain even after the baby is born. Usually, these cells mature by the time the child is 3 to 4 years old. But if this doesn’t happen, the cells might somehow begin to grow out of control, which might result in a Wilms tumor.

Changes in genes

Normal human cells grow and function based mainly on the information contained in each cell’s DNA. DNA is the chemical in each of our cells that makes up our genes, which control how our cells function. Genes are packaged in chromosomes (long strands of DNA). We normally have 23 pairs of chromosomes in each cell (with one set of chromosomes coming from each parent). We usually look like our parents because they are the source of our DNA. But DNA affects more than how we look.

Some genes control when our cells grow, divide into new cells, and die:

• Genes that help cells grow, divide, or stay alive are called oncogenes.
• Genes that slow down cell division or cause cells to die at the right time are called tumor suppressor genes.

Cancers can be caused by DNA changes (mutations) that turn on oncogenes or turn off tumor suppressor genes. 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, but most Wilms tumors don’t seem to be caused by inherited gene mutations. Instead, they seem to result from gene changes that occur early in a child’s life, perhaps even before birth.

Gene changes in Wilms tumors

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

• A small number of Wilms tumors have changes in or loss of the WT1 or WT2 genes, which are tumor suppressor genes found on chromosome 11. Changes in these genes 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.
• In a small number of Wilms tumors there is a change in a tumor suppressor gene known as WTX, which is found on the X chromosome.
• Another gene that is sometimes altered in Wilms tumor cells is known as CTNNB1, which is on chromosome 3.

It’s not clear exactly what causes these genes to be altered.

Several other gene or chromosome changes have been found in 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, 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 prevent these cancers.