on Tuesday, March 13, 2012
In a large-scale genome-sequencing study, researchers discovered mutations in neuroblastoma tumors that could aid the development of diagnostic tests and therapies.
A multicenter study has identified gene mutations that are common in teenagers and adults with advanced stages of neuroblastoma, a cancer that originates in nerve tissue. Published in the March 14 issue of the Journal of the American Medical Association, the findings could help guide the development of new diagnostic tests and therapies for neuroblastoma.
Usually diagnosed in children, neuroblastoma is the most common cancer among infants, but can also affect adolescents and young adults. However, the behavior of the disease varies according to age group.
For example, while neuroblastoma is often curable in infants and some children, most people who are diagnosed during adolescence or adulthood have a subtype of the disease, commonly described as indolent or chronic, which progresses slowly but is more difficult to cure.
“Currently, a patient’s age at the time of diagnosis is one of the most important factors that doctors take into account in estimating the patient’s long-term prognosis,” says pediatric oncologist Nai-Kong Cheung, who heads Memorial Sloan Kettering’s Neuroblastoma Program.
“The relationship between age and prognosis is well established,” he adds, “but the reason behind it has not been known.”
Now Dr. Cheung and his colleagues — in collaboration with investigators at the St. Jude Children’s Research Hospital and the Washington University School of Medicine — have identified a gene called ATRX that commonly is mutated in tumors from patients with neuroblastoma diagnosed as adolescents and young adults.
“Mutations in ATRX might explain why tumors behave differently across age groups,” he says.
The researchers sequenced and analyzed all the DNA in tumors from more than 100 neuroblastoma patients who had been treated at Memorial Sloan Kettering — including infants, children, and adults.
They found mutations in the ATRX gene in 44 percent of patients 12 years or older at the time of diagnosis. By comparison, ATRX mutations were not found in infants and identified in only 17 percent of children between the ages of 18 months and 12 years. The mutations were present only in tumor cells, and not in the patients’ noncancerous cells.
Dr. Cheung is hopeful that the findings could lead to the development of genetic tests to inform treatment decisions in children with neuroblastoma.
“Eventually, doctors might be able to determine whether a child with an early-stage tumor has the chronic form of neuroblastoma,” he explains. “In the future, as more therapies become available, such tests could provide a way to determine what types of therapy an individual child might benefit from.”
In addition, he and his coworkers believe their findings might encourage scientists to investigate the how the ATRX gene functions in normal tissues and in tumors. Ultimately, such basic research could lead to treatment innovations in neuroblastoma and other cancers.
“Recently, mutations in ATRX have been found in several cancer types, including pancreatic endocrine tumors and high-grade brain tumors, as well as neuroblastoma,” Dr. Cheung notes. “We suspect that the mutations might be good therapeutic targets.”
He adds that the study was made possible by Memorial Sloan Kettering’s extensive neuroblastoma tumor bank, a unique resource for genetic studies of the disease.
“Our physicians see both children and adults with neuroblastoma, and have been carefully collecting and annotating tumor samples for more than two decades,” he notes. “Thanks to all the patients and their families who have given us their consent to do this important research, we are in a better position than ever before to advance our understanding of the disease, and to find new ways to control it.”