Study finds association between genetic mutation and age at diagnosis for common childhood cancer

March 13, 2012, JAMA and Archives Journals

Certain mutations of the gene ATRX were associated with age at diagnosis in children and young adults with advanced-stage neuroblastoma, a cancer that grows in parts of the nervous system, according to a study in the March 14 issue of JAMA.

Neuroblastoma is the most common extracranial (outside the cranium) solid of childhood and accounts for 15 percent of all cancer-related deaths in children. "Half of the patients (50 percent) with present with metastatic disease; with current treatment approaches, the at has proven to be one of the most powerful predictors of outcome. The of overall is 88 percent in infants [age: less than 18 months at time of diagnosis], 49 percent in children [age: 18 months – less than 12 years], and only 10 percent in adolescents or [age: 12 years or older]," according to background information in the article. "Genetic associated with neuroblastoma and its clinical course are not completely understood."

Nai-Kong V. Cheung, M.D., Ph.D., of the Memorial Sloan-Kettering Center, New York, and colleagues conducted a study to identify genetic mutations that are associated with age at diagnosis in patients with metastatic neuroblastoma. Whole genome sequencing was performed of DNA from diagnostic tumors and their matched germlines (those cells of an individual that have material that could be passed to offspring) from 40 patients with metastatic neuroblastoma obtained between 1987 and 2009. Age groups at diagnosis included infants (0-<18 months), children (18 months-<12 years), and adolescents and young adults (12 years or older). To confirm the findings from this cohort (the discovery cohort), validation testing using tumors from an additional 64 patients obtained between 1985 and 2009 also was performed.

The researchers found that all 5 samples from adolescents and young adult patients in the discovery cohort had ATRX mutations (100 percent), whereas no ATRX mutations were detected in 6 samples obtained from infants (0 percent); among the 29 children ages 18 months to 12 years, ATRX mutations were identified in 5 (17 percent), with 4 of 5 patients living at least twice as long as their time to first relapse. A significant association was observed for the discovery cohort between ATRX mutation and age group.

"In the validation cohort (n = 64), mutations in the ATRX gene were identified in 33 percent of tumors from patients in the adolescent and young adult group (9 of 27), in 16 percent of tumors from children (4 of 25), and in 0 percent of tumors from infants (0 of 12). In both cohorts (n = 104), mutations in the ATRX gene were identified in 44 percent of tumors from patients in the adolescent and young adult group (14 of 32), in 17 percent of tumors from children (9 of 54), and in 0 percent of tumors from infants (0 of 18)," the authors write. Analysis of the data indicated a significant association between ATRX mutation and age of disease diagnosis.

"These results suggest that inactivation [disruption] of the ATRX pathway correlates with older age at diagnosis and may provide a molecular marker and potential therapeutic target for neuroblastoma among adolescents and young adults," the researchers write.

The authors add that future studies should focus on assembling larger international cohorts of patients to study the short-term and long-term outcomes for patients with neuroblastoma across all age groups with ATRX mutations compared with those without ATRX mutations. "These data may be useful in defining a more relevant age cutoff for the adolescent and young adult group and help to identify more effectively those patients who will have an increased risk of developing chronic or indolent [protracted] neuroblastoma."

Explore further: Common genetic variants associated with development of high-risk neuroblastoma

More information: JAMA. 2012;307[10]:1062-1071.

Related Stories

Common genetic variants associated with development of high-risk neuroblastoma

September 19, 2011
Patients with a high degree of African ancestry had a greater incidence of high-risk neuroblastoma and poorer outcomes, according to preliminary results presented here at the Fourth AACR Conference on The Science of Cancer ...

New therapy for childhood neuroblastoma proves feasible and safe

June 29, 2011
A new treatment option may soon be available for children with neuroblastoma according to research published in the July issue of The Journal of Nuclear Medicine. The study tested the principle that combined positron emission ...

Recommended for you

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

Researchers develop swallowable test to detect pre-cancerous Barrett's esophagus

January 17, 2018
Investigators at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center have developed a simple, swallowable test for early detection of Barrett's esophagus that offers promise ...

Scientists zoom in to watch DNA code being read

January 17, 2018
Scientists have unveiled incredible images of how the DNA code is read and interpreted—revealing new detail about one of the fundamental processes of life.

Presurgical targeted therapy delays relapse of high-risk stage 3 melanoma

January 17, 2018
A pair of targeted therapies given before and after surgery for melanoma produced at least a six-fold increase in time to progression compared to standard-of-care surgery for patients with stage 3 disease, researchers at ...

Dulling cancer therapy's double-edged sword

January 17, 2018
Researchers have discovered that killing cancer cells can actually have the unintended effect of fueling the proliferation of residual, living cancer cells, ultimately leading to aggressive tumor progression.

T-cells engineered to outsmart tumors induce clinical responses in relapsed Hodgkin lymphoma

January 16, 2018
WASHINGTON-(Jan. 16, 2018)-Tumors have come up with ingenious strategies that enable them to evade detection and destruction by the immune system. So, a research team that includes Children's National Health System clinician-researchers ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.