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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
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