Understanding of Neuroblastoma Risk Enhanced
Two studies looking at the genetic causes of neuroblastoma have unlocked much of the mystery surrounding why it arises in some children and not in others. This complex and puzzling cancer is the most common solid cancer of early childhood, causing 15 percent of all childhood cancer deaths. Pulling from the strengths of the CHOP Research powerhouses the Center for Applied Genomics and the Center for Childhood Cancer Research, the studies used DNA samples collected from around the world by the Children’s Oncology Group to better define the genetic landscape of neuroblastoma.
In the largest pediatric oncology gene study ever conducted, led by John Maris, MD, chief of the Division of Oncology and director of the Center for Childhood Cancer Research, the team performed a genome-wide association study to compare DNA from neuroblastoma patients with DNA from healthy children. The team found that common variants in the gene BARD1 increase a child’s susceptibility to a high-risk form of neuroblastoma. Published in Nature Genetics, this study has opened the door for research to understand the mechanism by which BARD1 gene variants act on developing nervous system cells to give rise to cancer during fetal or early development.
A second genome-wide study, spearheaded by Sharon Diskin, PhD, Division of Oncology, and published in Nature, found that an inherited 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. The chromosome region where the CNV is located, 1q21.1, contains a large family of genes that are involved in the development of the nervous system. The CNV identified in the study changes how much of one particular gene is made within normal nerve and neuroblastoma cells. In addition to the impact this has on neuroblastoma research, this study is notable in the field of genome-wide analysis as a whole, as it was the first to show a specific CNV predisposes people to cancer and has set the stage for studies to identify the mechanisms of how CNVs may increase the risk of cancer.
Diskin SJ, Hou C, Glessner JT, Attiyeh EF, Laudenslager M, Bosse K, Cole K, Mossé YP, Wood A, Lynch JE, Pecor K, Diamond M, Winter C, Wang K, Kim C, Geiger EA, McGrady PW, Blakemore AI, London WB, Shaikh TH, Bradfield J, Grant SF, Li H, Devoto M, Rappaport ER, Hakonarson H, Maris JM. Copy number variation at 1q21.1 associated with neuroblastoma. Nature. 2009 Jun 18;459(7249):987-91.