Gene Findings Unlocking Reasons for Neuroblastoma Risk
–Whole-Genome Searches Are Revealing Secrets of a Childhood Cancer–
Originating in the peripheral nervous system, neuroblastoma is the most common solid cancer of early childhood and causes 15 percent of all childhood cancer deaths.
“Only two years ago we had very little idea of what causes neuroblastoma,” said study leader
In the largest gene study to date in pediatric oncology, Maris’s study team performed a genome-wide association study to discover that common variants in the gene BARD1 increase a child’s susceptibility to a high-risk form of neuroblastoma.
A second genome-wide study found that a copy number variation (CNV) — a missing stretch of DNA — along a structurally weak location on chromosome 1 plays an important role in the development of neuroblastoma. Although CNVs have received much attention from genetics researchers over the last several years, this study was the first example of a specific CNV that predisposes people to cancer.
The BARD1 study was published online in Nature Genetics on
The BARD1 gene had already attracted attention from oncology researchers because it is associated with the gene BRCA1, which was the first discovered familial breast cancer gene. “Researchers have suspected that variants in BARD1 also increased the risk of breast cancer, but no one has found compelling evidence of this,” said Maris. “Instead, surprisingly, our genome-wide association studies found that BARD1 is a susceptibility gene for neuroblastoma, and perhaps other cancers as well.”
Maris added that researchers are now working to understand the mechanism by which BARD1 gene variants act on developing nervous system cells to give rise to cancer during fetal or early childhood development.
Maris’s second study, spearheaded by Dr.
This study, Maris added, opens up a new area for studying the mechanisms of how CNVs may increase the risk of cancer.
The current findings build on 2008 studies by Maris’s lab, one identifying the ALK gene as the major gene predisposing patients to the rare familial form of neuroblastoma, and the other identifying a region of chromosome 6 that increases the risk of the nonhereditary form of the disease. The ALK gene discovery has already led to a clinical trial led by Dr.
As gene studies continue to better define the genetic landscape of neuroblastoma, added Maris, pediatric oncologists can better develop more precise targeted treatments to improve survival and quality of life for children with this complex disease. The Cancer Center at Children’s Hospital has one of the nation’s largest research and clinical programs in pediatric oncology.
DNA samples for both studies were provided by the Children’s Oncology Group, a multicenter collaborative research organization in which Maris chairs the committee overseeing basic and clinical research in neuroblastoma. A variety of funding sources supported both studies, including the National Institutes of Health, the Alex’s Lemonade Stand Foundation, the Evan Dunbar Foundation, the Rally Foundation, the Andrew’s Army Foundation, the Abramson Family Cancer Research Institute and the Giulio D’Angio Endowed Chair.
Maris is also on the faculty of the
Capasso et al, “Common variations in BARD1 influence susceptibility to high-risk neuroblastoma,” Nature Genetics, published online
Diskin et al, “Copy number variation at 1q21.1 associated with neuroblastoma,” Nature, published
About The Children’s Hospital of
The Children’s Hospital of
Contact: Rachel Salis-Silverman The Children's Hospital of Philadelphia Phone: (267) 426-6063 Salis@email.chop.edu
SOURCE The Children’s Hospital of