The causes of neuroblastoma are not completely known. However, researchers have found important differences between neuroblastoma cells and the normal neuroblasts (primitive nerve cells) they develop from. They have also found differences between neuroblastomas likely to respond to treatment and those that have a poor prognosis (outlook). These differences (prognostic markers) are useful in selecting treatment for some patients (see the sections, "How is neuroblastoma diagnosed?" and "How is neuroblastoma treated?").

For many years, scientists have known that both nerve cells and cells of the medulla (center) of the adrenal gland develop from cells in the fetus called neuroblasts. Many researchers think that neuroblastomas develop when normal fetal neuroblasts fail to become mature nerve cells or adrenal medulla cells. Instead, they continue to grow and divide.

Neuroblasts may not have completely matured by the time a baby is born. In fact, studies have shown that small clusters of neuroblasts are common in infants less than 3 months old. Most of these eventually mature into nerve cells or simply disappear and do not form neuroblastomas. Sometimes, neuroblasts remaining in very young infants continue to grow and then form tumors and may even spread to other parts of the body. But many of these tumors will still eventually mature into nerve tissue or disappear.

However, as children get older, it becomes less likely that these cells will mature and more likely that they will continue to grow into a cancer. By the time neuroblastomas are large enough to be felt or cause symptoms, most can no longer mature on their own and will grow and spread unless treated.

This failure to mature and to stop growing is due to abnormalities in the DNA of neuroblasts. DNA is the substance that carries the instructions for nearly everything our cells do. DNA is found in each cell's nucleus (control center), in long string-like structures called chromosomes. We usually look like our parents because they are the source of our DNA, but DNA affects more than how we look. It affects many aspects of how our body functions, including our risks for developing certain diseases such as some kinds of cancer.

The information contained in DNA is divided into packets called genes. Some genes contain instructions for controlling when our cells grow, divide, and die. Certain genes that speed up cell division are called oncogenes. Others 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.

Neuroblastoma cells sometimes contain higher than normal levels of an oncogene called MYCN, which may be responsible for their uncontrolled growth.

A tumor suppressor gene called TrkA is sometimes less active than usual in neuroblastoma cells, which may be another reason for uncontrolled growth.

In most cases there are changes in some of the chromosomes in neuroblastoma cells that likely affect other genes. Scientists are still trying to determine which genes are affected by these chromosome changes, as well as how these changes might affect the growth of neuroblastoma cells.

Some people who develop cancer have DNA mutations they inherited from a parent, which increases their risk for the disease. In rare cases, neuroblastoma seems to be due to inherited gene changes. Recent research suggests that inherited mutations in the ALK gene may account for most cases of hereditary neuroblastoma.

Still, the great majority of neuroblastomas are not caused by inherited DNA mutations. They are the result of mutations acquired early in the child's lifetime. These changes are present only in the patient's cancer cells and will not be passed on to his or her children.

Although the causes of mutations responsible for certain adult cancers are known (for example, cancer-causing chemicals in cigarette smoke), the reasons for DNA changes that cause neuroblastomas are not known.

Last Medical Review: 10/22/2008
Last Revised: 10/22/2008