Genetic variation linked to neuroblastoma

Neuroblastoma is among the most common childhood cancers, with the majority of cases arising in individuals under 2 years of age. It is a neuroendocrine cancer that arises within the developing neural crest of the sympathetic nervous system. A research study at the Children’s Hospital of Philadelphia and the University of Pennsylvania published in the journal Nature (18 Jun 2009, Vol 459, pp 987-991) discovered evidence for a chromosome 1q21.1 copy number variation linked to higher incidences of neuroblastoma. This particular copy number variation, or CNV, indicates that a section of genetic material on the first human chromosome was deleted.

A genome-wide analysis was performed using single nucleotide polymorphisms (SNPs; variations in the DNA sequence at one base pair) in healthy subjects and neuroblastoma patients to track genomic variations between the two groups. This investigation revealed a seven-SNP deletion at position 1q21.1 in significantly higher frequency in the neuroblastoma group. This deletion at position 1q21.1 was discovered in nearly 100% of both parents of each individual patient, indicating that the 1q21.1 deletion is likely inherited.

To further validate an association between the 1q21.1 CNV and cases of inherited neuroblastoma, these researchers performed quantitative PCR (qPCR) and fluorescence in situ hybridization (FISH) on 46 neuroblastoma patients. In qPCR, RNA primers amplify a specified region of DNA to reveal the size and/or genomic sequence within that region, while FISH analysis uses fluorescent probes to mark genomic positions on whole chromosomes. In this study, 100% of those patients examined had the 1q21.1 CNV deletion. The authors discovered a new gene similar in sequence to several characterized NBPF (neuroblastoma breakpoint family) genes within this region, named NBPF23, which is upregulated during early sympathicordial neurodevelopment in normal fetal brain tissues.

As scientists have learned in the past decade (with the help of the sequenced human genome), genomic variation often can predispose individuals to certain diseases, including autism, schizophrenia, and certain types of cancer, as described here for familial neuroblastoma. So if the human genome could tell us what diseases we, or our children, might contract later in life, do we want to know? What if treatment is available to improve our quality of life, or even provide a cure? What if there isn’t?