The causes of neuroblastoma are not completely known. But 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 (known as prognostic markers) are useful in selecting treatment for some patients (see the section, "How is neuroblastoma staged?").

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 in babies by the time they are born. In fact, studies have shown that there are small clusters of neuroblasts in the adrenal glands of some 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 go away on their own.

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 abnormal DNA in the neuroblasts. DNA is the chemical in each of our cells that makes up our genes -- the instructions for how our cells function. 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 can also influence our risk for developing certain diseases, such as some kinds of cancer.

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.

For example, 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, some of the chromosomes in neuroblastoma cells have changes 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 development. These changes are present only in the cancer cells, so they will not be passed on to his or her children.

Although some of the causes of DNA mutations in 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: 11/23/2009
Last Revised: 11/23/2009