Researchers Find Gene Mutations Linked to Age at Neuroblastoma Diagnosis

Pictured: Nai-Kong Cheung

Nai-Kong Cheung, Neuroblastoma Program Head

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.

We are in a better position than ever before to advance our understanding of neuroblastoma.
Nai-Kong Cheung Pediatric Oncologist

“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.”


Commenting is disabled for this blog post.

I would love to be kept informed of the progression in research for Neuroblastoma. My daughter was dignosed in 2001 with adrenal/juvenille/mature cancer at 19 months. I have been active in the research and education of newly dignaosed parents and help them to cope with this childhood cancer. I live in Akron, Ohio.

Thank you. Would snap frozen tissue from virgin neuroblastoma of 2 year old with bone met and no bone marrow met. be analyzed genetically by you if we send it to you from Bay Area, Ca. We would benefit fromt he genetic analysis and you would add to your data base for present and future studies.

Samira, we will send information about this to the email address that you provided. Thank you for your comment.

I also am interested in everything about neuroblastoma....even though my child past away from this cancer at the age of two years ....I find myself still unable to except more couldn't have been done ....its been five years already since I lost him ...but the dr ,s said he had the worst kind there was ...special neuroblastoma stage 3 they said ...after they removed his kidney and part of the tumor ....they couldn't get it all ....they said they never saw a tumor like his ...very progressive...anyway I wish I could have had known about this dr ...and had someone research his tumor since its was so bad ....anyway keep up the good work I will always be watching for the day they can find a cure for neuroblastoma ...and thank you

absolutely wonderful information ....

Doctor Cheung,
I'd like to thank you for your passion and persistence and continued tireless research regarding Neuroblastoma. It has been intriguing to steadily see you and team of researchers pursue unlocking gene's that with help our children. God bless you and all of our families for dedication and donations for clinical trials. Prayer's to families who have lost their battle.

Is there a way to Directly donate funds to help continue the advancements in finding a cure for neuroblastoma in infants and children? I understand that only 4% of funding goes towards research in pediatric cancers. I am saddened to hear about all the deaths that occur in young children because of cancer and although I cant bring them back I hope their parents can find at least some solace knowing that their children touched many hearts and in turn have people
wanting to help in any way they can to help beat this disease.

Dear Daniela, our Development office would be happy to answer your questions about how your donation can directly support a specific area of research at Memorial Sloan Kettering. You may reach out to them at 1-866-815-9501 or [email protected]. For more information, please visit Thank you for your thoughtful comment.

I am interested in more information. My son is currently NED, 24+ post SCT. He is up for Radiation and immunotherapy next.

I would be interested in knowing about any new & ongoing research/ breakthroughs regarding neuroblastoma. My daughter was diagnosed at age 7-1/2 & died at age 10 in 1987 from this disease. She was treated at MSK & sadly back then it was considered 'low man on the totem pole' in regards to concern, research & funding to help these children. In addition, my daughter was rejected by St. Jude's because of her age when diagnosed. It is encouraging to see more recognition & research is being done to help. It is still very important to me. Thank you to those dedicating their knowledge & time to help in this very difficult fight.

Dear Deena, we are sorry for your loss. You may be interested in reading this blog post about a new drug. You may also like to read this interview with two of our neuroblastoma experts.

Thank you for sharing your experiences and best wishes to you.