DNA Region on Chromosome 1 Is Linked to Neuroblastoma - National Cancer Institute

DNA Region on Chromosome 1 Is Linked to Neuroblastoma

The Bottom Line

Results of a genome-wide association study indicate that a specific region on human chromosome 1 is associated with the development of neuroblastoma, a childhood cancer that that forms in the adrenal glands and nerve tissue.

This chromosome region contains a section of DNA that can vary in copy number from person to person, and neuroblastoma patients were more likely than control subjects to have fewer than normal copies of this DNA.

A new gene was identified in this DNA section that appears to play a role in the development of the brain and nerve tissue.

The Whole Story

Neuroblastoma is the most common extracranial (non-brain) solid tumor that occurs in childhood. Approximately two-thirds of patients diagnosed with this tumor are younger than 5 years of age. It occurs most frequently in the adrenal glands, but it can also develop in nerve tissue in the abdomen, chest, pelvis, and neck. On the basis of age at diagnosis, the stage of the tumor, and the tumor's genetic and biological characteristics, patients are divided into three risk groups: low, intermediate, and high. More than 90 percent of patients with low-risk neuroblastoma can be cured of their disease. Patients with intermediate-risk neuroblastoma generally have a cure rate of 70 percent to 90 percent. For children with high-risk neuroblastoma, long-term survival ranges from 10 percent to 40 percent.

Approximately one percent of neuroblastoma cases of are classified as familial cancers, and it has been reported that inheritance of a single mutant copy of a gene called ALK, which is located on chromosome 2, causes most of these tumors. The remaining cases are classified as sporadic neuroblastomas and occur in patients whose families have no history of the disease. Nonetheless, it is believed that commonly occurring, inherited variations in DNA can contribute to the development of sporadic neuroblastomas.

To identify regions in germline DNA that are associated with the risk of developing neuroblastoma, scientists conducted a genome-wide association study, or GWAS, in which white blood cell DNA (that is, non-tumor DNA) from 846 patients with neuroblastoma and 803 healthy control subjects was compared. The researchers identified a specific section of DNA on chromosome 1 that can vary in copy number from person to person. Most people had two copies of this DNA section: one on the chromosome 1 they inherited from their mother and the other on the chromosome 1 they inherited from their father. However, some patients and control subjects had fewer than two copies of the DNA in this section (they had DNA deletion), whereas others had more than two copies (they had DNA duplication). Overall, DNA deletion was found to be much more common in neuroblastoma patients than in control subjects. The researchers confirmed these findings by conducting additional studies involving another 595 patients with neuroblastoma and 3,357 control subjects.

When the scientists examined this DNA section more closely, they identified a new gene, called NBPF23, whose expression is influenced by variations in DNA copy number. They also showed that NBPF23 is expressed preferentially in the developing brain and nerve tissue of the human fetus, which is what would be expected for a gene that plays a role in neuroblastoma development. Presumably, a lower-than-normal copy number of NBPF23 results in reduced expression of this gene and contributes to the development of neuroblastoma.

The research team is continuing its efforts to understand neuroblastoma and identify other DNA variations that contribute to its development.

Reference: Diskin SJ, Hou C, Glessner JT, et al. Copy number variation at 1q21.1 associated with neuroblastoma. Nature 2009; 459(7249):987-991.
Copy number variation at 1q21.1 associated with ne... [Nature. 2009] - PubMed result


DNA Region on Chromosome 1 Is Linked to Neuroblastoma - National Cancer Institute