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Chromosome Deletion Predicts Aggressive Neuroblastoma

When genes are deleted on a particular section of chromosome 11, the result is an aggressive form of the childhood cancer neuroblastoma. A new study suggests that detecting this genetic deletion during the initial evaluation of children with neuroblastoma may indicate to physicians that they should recommend a more aggressive regimen of chemotherapy to fight the cancer.

Edward F. Attiyeh, M.D., a pediatric oncology fellow at The Children's Hospital of Philadelphia, reported on a study of 915 patients in a presentation today at the American Society of Clinical Oncology annual meeting in Orlando, Fla. The patients were children with primary neuroblastoma treated at Children's Oncology Group (COG) centers. The COG is a National Institutes of Health-funded multicenter clinical research organization that supports clinical trials for pediatric cancer patients.

Neuroblastoma, which accounts for 10 percent of all pediatric cancers, often occurs as a solid tumor in a child's abdomen or chest. Some cases of neuroblastoma are low risk, and resolve after surgeons remove the tumor. Other cases are more aggressive, and are more likely to resist initial treatment, or to cause a relapse. Identifying the correct risk level allows doctors to treat aggressive cancers appropriately, while not subjecting children with low-risk cancer to overtreatment.

Oncologists know that amplification, an abnormal increase in the number of copies, of a cancer-causing gene called MYCN heralds a high-risk, aggressive cancer. However, a significant number of neuroblastomas are aggressive without having amplified MYCN. "The deletion of genetic material on chromosome 11 may account for a significant percentage of these high-risk neuroblastomas," said Dr. Attiyeh.

It is unknown what causes the deletion of genes on chromosome 11, at a location designated chromosome 11q23. However, the loss of material at that site apparently removes the protective effect of a tumor suppressor g ene, and thereby allows the tumor to grow. Patients in the study with the chromosome deletion had a three-year overall survival rate of 66 percent, compared to 83 percent for patients without the deletion.

Dr. Attiyeh's research abstract received top honors at the ASCO meeting, by being named the top abstract among more than 100 submitted by oncology fellows. It also received a second award, as the highest-ranking abstract in pediatric cancer research. Dr. Attiyeh works in a comprehensive neuroblastoma research program at Children's Hospital, directed by John M. Maris, M.D., the senior author of the abstract.

Co-authors of the study, in addition to Drs. Attiyeh and Maris, included Katherine K. Matthay, M.D., of the University of California, San Francisco; and Yael P. Mosse, M.D., of The Children's Hospital of Philadelphia.


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Source:Children's Hospital Of Philadelphia


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