Do We Know 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.
Both nerve cells and cells of the medulla (center) of the adrenal gland develop from neuroblasts in the fetus. 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 matured completely 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 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 – the instructions for 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. 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 that turn on oncogenes or turn off tumor suppressor genes. These gene changes can be inherited from a parent (as is sometimes 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.
In rare cases, neuroblastoma seems to occur because of gene changes inherited from a parent. Inherited changes in the ALK oncogene seem to account for most cases of hereditary neuroblastoma. A small number of inherited neuroblastomas are caused by changes in PHOX2B, a gene that normally helps nerve cells mature.
Still, most neuroblastomas are not caused by inherited DNA changes. They are the result of gene changes that happen early in the child’s development, often before birth. 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 (non-inherited) neuroblastomas have changes in the ALK gene. But in many neuroblastomas the exact genes affected are not known.
Some gene changes seem to affect how quickly a neuroblastoma is likely to grow. For example, neuroblastoma cells sometimes have extra copies of an oncogene called MYCN, which is often a sign that the tumor will grow quickly and be harder to treat. On the other hand, the NTRK1 gene (which makes the TrkA protein) is often overactive in the cells of neuroblastomas that have a better outlook. Researchers recently found that 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 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 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.
Last Medical Review: March 14, 2014 Last Revised: January 22, 2016