A study reports that a loss of genes on chromosome 1 or chromosome 11 raises the risk of death from the children's cancer neuroblastoma, even when other indicators seem to point to a lower-risk form of the disease.
" Identifying more accurate risk levels of this cancer allows doctors to treat aggressive types of the cancer appropriately, while not subjecting children with lower-risk cancer to overtreatment," said study leader John Maris, of The Children's Hospital of Philadelphia.
The study is published in the New England Journal of Medicine.
The research team analyzed tumor samples from 915 children with neuroblastoma.
Neuroblastoma is the most common cancer in infants, accounting for 10 percent of all pediatric cancers, but its course is not easily predictable. Often occurring as a solid tumor in a child's abdomen or chest, some cases spontaneously resolve even without surgery, while others are particularly aggressive -- resisting initial therapy, or causing a relapse.
Based on previous studies by Maris and other researchers that identified abnormalities on chromosomes 1 and 11 as contributing to high-risk neuroblastoma, the current research team analyzed gene defects in a large series of neuroblastoma tumors. " We found that loss of genetic material on chromosome bands 1p36 and 11q23 was strongly linked to high-risk neuroblastoma," he said. He added that the survival rate was worse when the loss of material was unbalanced on chromosome 11, occurring on the chromosome's "q" arm but not on its shorter "p" arm.
Researchers call this deletion of one copy of a chromosome "loss of heterozygosity" ( LOH ). The unbalanced 11q LOH and the 1p36 LOH were independent markers of worse outcome for patients, regardless of other prognostic clues. For instance, unbalanced 11q LOH occurs almost always in tumors not showing amplified copies of the MYCN gene.
" Children known to have MYCN amplification are more likely to already be receiving the most aggressive therapy," said Maris. " However, it is important to look for 1p36 LOH and unbalanced 11q LOH in children with localized disease without MYCN amplification. Patients having one or both of these deletions may benefit from more intensive early treatment such as chemotherapy. If we can correctly detect risk factors at diagnosis, we can tailor their treatment accordingly."
Based on these findings, the Children's Oncology Group plans to add the status of chromosome arms 1p and 11q to its list of prognostic markers in evaluating children with neuroblastoma. This information will be incorporated into future clinical trials, as researchers analyze new treatments for this pediatric cancer. "As we continue to develop better treatments, we hope to combine those treatments with more refined diagnoses, so we can identify and then treat high-risk cancers earlier, before they can progress or relapse," says Maris.
The research team will be conducting further work on these particular genetic abnormalities. " Our hope is to identify one or more genes on chromosome arm 11q that are involved in the development of aggressive neuroblastoma, and then use those specific genes as targets for therapy," said lead author Edward F. Attiyeh, also of The Children's Hospital of Philadelphia.
Source: Children's Hospital of Philadelphia, 2005