For distinguishing between disease types, the key is in the genes
Seven hundred infants and young children in the United States this year will develop neuroblastoma, a cancer of certain nerve cells and the adrenal gland. Some of them will have a variety in which the neuroblastoma cells carry a normal or slightly increased complement of a key gene; the rest will have a type of the disease where the gene is multiplied dozens of times over.
The two forms of neuroblastoma are impossible to distinguish by their symptoms or their appearance under a microscope. But it's crucial that doctors be able to tell them apart because they're treated quite differently. Infants with one variety can almost always be cured with surgery and a relatively mild course of chemotherapy (and some require surgery alone). Those with the other type have less than a 50 percent chance of survival, even with high-dose chemotherapy and bone marrow transplantation.
Identical as they may appear on the surface, the two varieties are not quite twins. The only way to tell them apart is to remove a tumor sample from a patient and examine the genetic content of its cells — does it have many copies of the critical gene, or only a few?
That kind of high-tech testing is difficult to perform in most hospitals, which may see only one or two neuroblastoma patients a year. What's needed is a central laboratory where neuroblastoma samples from around the country can be analyzed by people experienced in genetic-testing techniques.
"Our new lab represents a useful way to bring the science of molecular genetics to patients."
mdash; Thomas Look, M.D., director, Center for Pediatric Cancer Genetics
Such a facility now exists at Dana-Farber, under the direction of Thomas Look, M.D., who operated a similar center at St. Jude Children's Research Hospital in Memphis. Known as the Center for Pediatric Cancer Genetics and staffed by clinical specialists in cytogenetics Lisa Moreau and Susan Rowe, the new facility will ensure that neuroblastoma patients across the country have access to the highest-quality diagnostic services. The center was developed in conjunction with the Institute's Center for Fanconi Anemia (a rare disorder that places patients at risk for bone marrow failure and cancer), led by Alan D'Andrea, M.D.
"Advances in testing mean that in more than 95 percent of cases, we can quickly and accurately determine the type of neuroblastoma a child has," Look says. "That information, provided promptly to a child's physician, is critical to deciding the proper course of treatment."
FISHing for genes
Thomas Look, M.D.
Neuroblastoma is the second-most common malignant solid tumor (after brain tumors) in infants and young children. To determine which type of the disease a patient has, investigators focus on a gene called MYCN. Using technology known as Fluorescence In Situ Hybridization (FISH), they're able to determine how many copies of MYCN are in a patient's neuroblastoma cells.
Infants whose tumor cells contain a normal number of copies of the gene have a much better prognosis than those with many copies, even in cases where the disease has spread to the liver, bone marrow, bones, and eye socket. More than 90 percent of the time, patients with normal MYCN genes can be cured with a six-month course of chemotherapy given on an outpatient basis. When a patient is found to have many copies, a different course of treatment is called for: aggressive combinations of chemotherapy agents, total body irradiation, and sometimes a double stem cell transplant — a regimen being developed by Dana-Farber's Lisa Diller, M.D.
"It's impossible to chart a 'middle ground' between these two treatment options, so physicians must know the MYCN status of the tumor before starting treatment," Look says.
With the opening of the Center for Pediatric Cancer Genetics, physicians across the country are able to send tumor samples overnight to Dana-Farber for analysis. The FISH test takes only a few days to complete, enabling doctors to begin therapy within a week of the initial surgery.
"The new lab was made possible by the support of the Friends of Dana-Farber Cancer Institute and the National Institutes of Health," Look says. "It represents a useful way to bring the science of molecular genetics to patients' bedsides, even before the 'magic bullets' we're all working to develop become a reality."
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