Genome-Wide Study Reveals Clues to Neuroblastoma Susceptibility

Common copy number variations (CNVs), DNA abnormalities that substantially contribute to genetic diversity, have been linked to the development of the deadly form of childhood cancer, neuroblastoma.

To study the possible roll of CNVs in human cancer a multi-institutional team of investigators performed a genome-wide association study of CNVs in the childhood cancer neuroblastoma, a disease in which single nucleotide polymorphism variations are known to influence susceptibility.

The team first genotyped 846 Caucasian neuroblastoma patients and 803 healthy Caucasian controls for about 550,000 single nucleotide polymorphisms, and performed a CNV-based test for association. Significant observations were then repeated in two independent sample sets comprised of a total of 595 cases and 3,357 controls. CNV data was validated by quantitative polymerase chain reaction, fluorescent in situ hybridization, and analysis of matched tumor specimens.

Results published in the June 18, 2009, online edition of the journal Nature revealed that a common CNV at chromosome 1q21.1 associated with neuroblastoma. A previously unknown transcript within the CNV was found that showed high sequence similarity to several neuroblastoma breakpoint family (NBPF) genes and represented a new member of this gene family (NBPF23). This transcript was preferentially expressed in fetal brain and fetal sympathetic nervous tissues, and the expression level was strictly correlated with CNV state in neuroblastoma cells.

"Only two years ago we had very little idea of what causes neuroblastoma," said senior author Dr. John J. Maris, professor of oncology at the Children's Hospital of Philadelphia (PA, USA). "Now we have unlocked a lot of the mystery of why neuroblastoma arises in some children and not in others."

The research teams that participated in this study are members of the [U.S.] National Institutes of Health (Bethesda, MD, USA) Children's Oncology Group, which performs clinical trials, collects specimens, and performs statistical analysis related to pediatric cancers.

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Children's Hospital of Philadelphia
National Institutes of Health