What Causes Neuroblastoma?

The causes of most neuroblastomas are not known. But researchers have found important differences between neuroblastoma cells and the normal neuroblasts (early forms of nerve cells) from which they develop. They have also found differences between neuroblastomas that are likely to respond to treatment and those that have a poor prognosis (outlook). These differences (known as prognostic markers) are sometimes helpful in choosing the best treatment.

How normal cells become neuroblastoma

Nerve cells and cells of the medulla (center) of the adrenal gland develop from neuroblasts in the fetus. These neuroblasts usually grow and change into mature nerve cells. Neuroblastomas develop when normal fetal neuroblasts do not become mature nerve cells or adrenal medulla cells. Instead, they continue to grow and divide.

Neuroblasts might not have matured completely in babies by the time they are born. Most of these eventually mature into nerve cells or simply die off and do not form neuroblastomas. Sometimes, neuroblasts remaining in very young infants continue to grow and then form tumors. Some can 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 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.

The failure of some neuroblasts to mature and to stop growing is due to abnormal DNA inside the cells. DNA is the chemical in each of our cells that makes up our genes, which control how our cells function. The DNA inside our cells is in long string-like structures called chromosomes.

Some genes contain instructions for controlling when our cells grow, divide into new cells, and die:

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

Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes. These gene changes can be inherited from a parent (as is rarely the case with childhood cancers), or they may happen during a person’s lifetime as cells in the body divide to make new cells.

In most cases, neuroblastoma cells have chromosome changes (such as having too many or too few chromosomes or missing part of a chromosome) that are likely to affect certain genes. Scientists are still trying to determine which genes are affected by these chromosome changes, as well as how these changes affect the growth of neuroblastoma cells.

Gene changes in neuroblastoma

In rare cases, neuroblastoma seems to occur because of gene changes inherited from a parent. Inherited changes in certain genes account for most cases of hereditary neuroblastoma:

  • ALK oncogene changes account for most cases of inherited neuroblastoma.
  • Changes in PHOX2B, a gene that normally helps nerve cells mature, account for a small number of inherited neuroblastomas.

Still, most neuroblastomas are not caused by inherited DNA changes. They are the result of gene changes that happen at some point during the child’s development, sometimes before birth. What causes these gene changes is not known. These changes are found only in the child’s cancer cells, so they will not be passed on to his or her children. For example, about 10% to 15% of sporadic (not inherited) neuroblastomas also have changes in the ALK gene. In many neuroblastomas the exact genes affected are not known.

Other gene changes seem to affect how quickly a neuroblastoma can grow. Here are some examples of gene changes in neuroblastoma cells and what they can mean about a child's neuroblastoma:

  •  Neuroblastoma cells sometimes have extra copies of an oncogene called MYCN amplification, which is often a sign that the tumor will grow quickly and be harder to treat.
  • When the NTRK1 gene (which makes the TrkA protein) is overactive in the cells of neuroblastomas, it can be sign that a child's neuroblastoma might have a better outlook.
  • Neuroblastoma cells in older children are more likely to have changes in the ATRX tumor suppressor gene. Tumors with this gene change tend to grow more slowly, but they are also harder to cure. This may help explain why younger children with neuroblastoma tend to do better long term than children who are older when they are diagnosed.

Researchers have found some of the gene changes that may lead to neuroblastoma, but it’s still not clear what causes these changes. Some gene changes may be inherited. Some might have unknown outside causes, but others could 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 neuroblastomas at this time, so it’s important to remember that there is nothing these children or their parents could have done to prevent these cancers.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

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Mosse YP, Laudenslager M, Longo L, et al. Identification of ALK as a major familial neuroblastoma predisposition gene. Nature. 2008;455:930–935.

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Last Revised: March 19, 2018

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