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Detailed Guide: Neuroblastoma
Do We Know What Causes Neuroblastoma?
The causes of neuroblastoma are not completely known. However, researchers have found certain important differences between neuroblastoma cells and the normal neuroblast cells they develop from. They have also found important differences between neuroblastomas likely to respond to treatment and those that have a poor prognosis (outlook for survival). Information about these differences (prognostic markers) is useful in selecting treatment for some patients (see sections on "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 produced by 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 formed into large string-like structures called chromosomes. We usually resemble our parents because they are the source of our DNA. However, DNA affects more than our outward appearance. It determines everything about 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. Changes in genes account for the growth of neuroblastoma cells. Some genes contain instructions for controlling when our cells grow and divide. Genes that promote uncontrolled cell division are called oncogenes. Neuroblastoma cells often contain higher than normal levels of an oncogene called MYCN, which may be responsible for their uncontrolled growth. Others that slow down cell division or cause cells to die at the right time are called tumor suppressor genes. A suppressor gene called TrkA is sometimes less active than usual, which is another reason for uncontrolled growth. Also, scientists have found that some of the chromosomes in neuroblastoma cells are defective, which may cause other unknown gene abnormalities. Cancers can be caused by DNA mutations (defects) that activate oncogenes or inactivate tumor suppressor genes.

Some people who develop cancer have DNA mutations they inherited from a parent, which increases their risk for the disease. Some researchers believe that the few familial cases of neuroblastoma are due to inherited tumor suppressor gene mutations.

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 mutations 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.

Revised: 08/04/2006
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