Neuroblastoma, Susceptibility To, 6

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Retrieved
2019-09-22
Source
Trials
Genes

For a general phenotypic description and a discussion of genetic heterogeneity of neuroblastoma, see NBLST1 (256700).

Mapping

Diskin et al. (2009) described the identification of a common copy number variation (CNV) at chromosome 1q21.1 associated with neuroblastoma in a discovery set of 846 Caucasian patients with neuroblastoma and 803 controls. The findings were confirmed in 2 independent replication sets comprising 595 cases and 3,357 controls. They first observed a hemizygous approximately 300-kb deletion at 1q21.1 that occurred in 15.6% of cases but in only 9.1% of controls. The difference in hemizygous deletion frequency was significant at p = 1.83 x 10(-19). The observed frequency of homozygous deletion was the same in cases and controls (1.3% overall). The maximal deletion size was about 143 kb; within this region, Diskin et al. (2009) identified a novel gene, NBPF23 (612970).

Molecular Genetics

In an analysis of 18 neuroblastomas, both tumors and cell lines, of known copy number at 1q21.1, Diskin et al. (2009) observed a clear correlation between CNV state and NBPF23 transcript expression. Notably, 2-copy samples clustered into 2 distinct expression classes (p = 0.007), with low and higher expression respectively, and these were thought to represent different 1q21.1 CNV genotypes. There are 2 possible CNV genotypes for 2 copy samples, which the authors referred to as 2:0 (cis) and 1:1 (trans) based on the number of NBPF23 copies present on each chromosome in a diploid genome. Two neuroblastoma samples in the low expression group could be demonstrated to have originated from the 2:0 constitutional CNV genotype because they had somatically acquired a gain of chromosome 1q (3 copies of chromosome 1q), yet there were 2 copies of the gene with heterozygous SNPs. Diskin et al. (2009) proposed a model in which NBPF23 expression is decreased when 2 NBPF23 copies are in the cis configuration as opposed to the trans configuration. The findings implicated this gene in the early tumorigenesis of neuroblastoma.