In children, neuroblastoma is the most prevalent extracranial (outside the cranium) solid tumor. The disease is responsible for 15% of all cancer-related deaths in children.
The researchers explain:
"Half of the patients (50 percent) with neuroblastoma present with metastatic disease; with current treatment approaches, the age at diagnosis has proven to be one of the most powerful predictors of outcome.
The probability of overall survival 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 of young adults [age: 12 or older. Genetic mutations associated with neuroblastoma and its clinical course are not completely understood."
Nai-Kong V. Cheung, M.D., Ph.D., of the Memorial Sloan-Kettering Cancer Center, New York, and colleagues set out to determine genetic variations that are linked to age at diagnosis in individuals with the disease.
After obtaining DNA from diagnostic tumors from 40 patients with metastatic neuroblastoma between 1987 and 2009, the researchers performed whole genome sequencing and their matched germlines (cells of a person that have genetic material that may be inherited by their children).
Age groups at diagnosis included:
- Infants aged 0 to 18 months
- Children aged 18 months to <12 years
- and adolescents and young adults aged 12+ years
The team found no ATRX variations in 6 samples derived from infants in the discovery cohort; all of the 5 samples obtained from adolescents and young adults had ATRX mutations (100%); and ATRX mutations were identified in 5 (17%) of the 29 children ages 18 months to 12 years, with 4 or 5 patients living at least two times longer as their time to first relapse.
"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)."
After evaluating the data, the researchers found a considerable link between age of disease diagnosis and ATRX mutation.
"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."
According to the researchers, future studies should involve larger international cohorts of patients in order to examine the short- and long-term outcomes for individuals with the disease across all age groups with ATRX variations and patients without ATRX variations.
The researchers conclude:
"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 of indolent [protracted] neuroblastoma."