Every year, about twenty children in Sweden are diagnosed with neuroblastoma. Neuroblastoma is a cancer originating from immature nerve cells that develop into cancer cells, forming solid tumors. The tumors grow in the sympathetic nervous system, which starts in the adrenal glands and follows the spine with its nerve fibers.
Most children develop the disease before the age of five, and some children develop it in the fetal stage. Of all childhood cancers, neuroblastoma has the lowest survival rate. Sofie Mohlin, an associate professor of molecular physiology at Lund University, and research group leader at Lund Stem Cell Center, has been researching neuroblastoma for several years:
"Genetic variations occur in tumours, which make them look different. Neuroblastoma is a cancer variant that is particularly heterogeneous, which also makes it more difficult to treat. Doctors usually have to use the majority of the drugs available, instead of being able to be more specific in their treatment. As a consequence, many children have severe side effects that they have to live with for the rest of their lives. Therefore, it is of the utmost importance to try to understand the disease in order to eventually be able to develop more targeted treatments."
MOXD1 - a brand new gene in neuroblastoma research
Sofie Mohlin's research group has now discovered that the gene MOXD1 is associated with neuroblastoma. Five percent of patients are found to be missing a piece of a chromosome where the MOXD1 gene is located. The research group has discovered that the gene has a very specific expression pattern in both healthy and diseased cells, where only specific types of cells express MOXD1. The gene is a so-called tumor suppressor whose task is to protect the cell from developing tumors. When the gene stops working for any reason, the regulatory mechanism is lost, resulting in a very aggressive form of neuroblastoma. The survival rate of children with this most aggressive form drops from an already low 30% to only around 10%.
"Previous studies have shown that neuroblastoma consists of two different cell populations with different characteristics. We show that "our" gene is only present in one of the cell populations, which could have major implications for the type of tumors that arise, how they behave and how they can be treated. Further studies are needed, but I think we have found a subgroup within neuroblastoma."
Deformed organs where neuroblastoma usually occurs
Sofie Mohlin hopes that a deeper understanding of the origin of the tumor during the fetal stage can be a step in identifying biomarkers that help in diagnosing and assessing the prognosis of the children.
"Excitingly, we have also seen that when healthy cells lose the function of the gene, the organs in which neuroblastoma usually arises are malformed. This is work that we are currently putting together for publication and that ties together how important it is to understand different cell populations during development, to see how certain types of healthy cells can lead to certain types of tumors. The next step is to try to understand exactly how the gene works and why it has such a strong significance for the healthy development of the fetus."
