MEMPHIS, Tenn., March 13, 2012 /PRNewswire/ --Researchers have identified the first gene mutation associated with a chronic and often fatal form of neuroblastoma that typically strikes adolescents and young adults. The finding provides the first clue about the genetic basis of the long-recognized but poorly understood link between treatment outcome and age at diagnosis.

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The study involved 104 infants, children and young adults with advanced neuroblastoma, a cancer of the sympathetic nervous system. Investigators discovered the ATRX gene was mutated only in patients age 5 and older. The alterations occurred most often in patients age 12 and older. These older patients were also more likely than their younger counterparts to have a chronic form of neuroblastoma and die years after their disease is diagnosed.

The findings suggest that ATRX mutations might represent a new subtype of neuroblastoma that is more common in older children and young adults. The work is from the St. Jude Children's Research Hospital Washington University Pediatric Cancer Genome Project (PCGP). The study appears in the March 14 edition of the Journal of the American Medical Association.

If validated, the results may change the way doctors think about this cancer, said co-author Richard Wilson, Ph.D., director of The Genome Institute at Washington University School of Medicine in St. Louis. "This suggests we may need to think about different treatment strategies for patients depending on whether or not they have the ATRX mutation," he said.

Neuroblastoma accounts for 7 to 10 percent of all childhood cancers and about 15 percent of pediatric cancer deaths. In about 50 percent of patients, the disease has already spread when the cancer is discovered.

For patients whose disease has spread, age has long been a powerful but perplexing predictor of treatment outcome. Currently 88 percent of patients age 18 months and younger become long-term survivors, compared to 49 percent of those ages 18 months through 11 years and only 10 percent of patients age 12 and older.

"Until now there was no understanding of the basis of this age-related risk, and no treatment has had an impact on the outcome," said Michael Dyer, Ph.D., a member of the St. Jude Department of Developmental Neurobiology and a Howard Hughes Medical Institute Early Career Scientist. He is the study's corresponding author. "The mutation we found is associated with patients in the older age group, but it also identifies for the first time a subset of younger patients who turned out to have an indolent form of neuroblastoma."

Researchers must now determine whether tumors with ATRX mutations behave the same way in both children and young adults, following a similarly indolent but often deadly course, said Nai-Kong Cheung, M.D., Ph.D., first author and head of the Neuroblastoma Program at New York's Memorial Sloan-Kettering Cancer Center.

St. Jude investigators have begun screening the hospital's library of federally approved drugs looking for evidence of activity against neuroblastoma cells with the ATRX mutation. Availability of more targeted therapies would likely spur efforts for early identification of patients with the ATRX mutation who have a chronic form of neuroblastoma and are unlikely to benefit from current therapies.

The rest is here:
Genome Sequencing Initiative Links Altered Gene to Age-Related Neuroblastoma Risk