“拷贝数变异”（CNVs）和“单核苷酸多态性”（SNPs）是人类表型变异的两个重要潜在来源。此前，只有SNPs被与癌症关联起来，但对胚系DNA剂量是人类多样性一个关键组成部分这一观点之认可程度的不断提高，使人们想到这样一个可能性：CNVs可能也影响对于这种癌症的易感性。
现在，Disklin等人报告说，染色体1q21.1上的一个常见CNV与儿童癌症“成神经细胞瘤”有关，而且这一CNV内的一个转录体（以前我们不知道的“成神经细胞瘤”断点家族基因NBPF23）也参与了肿瘤形成的早期阶段。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 459, 987-991 (18 June 2009) | doi:10.1038/nature08035
Copy number variation at 1q21.1 associated with neuroblastoma
Sharon J. Diskin1,2, Cuiping Hou1,3, Joseph T. Glessner3, Edward F. Attiyeh1,4, Marci Laudenslager1, Kristopher Bosse1, Kristina Cole1, Ya?l P. Mossé1,4, Andrew Wood1, Jill E. Lynch1, Katlyn Pecor1, Maura Diamond1, Cynthia Winter1, Kai Wang3, Cecilia Kim3, Elizabeth A. Geiger6, Patrick W. McGrady8, Alexandra I. F. Blakemore9, Wendy B. London8, Tamim H. Shaikh4,6, Jonathan Bradfield3, Struan F. A. Grant3,4,6, Hongzhe Li7, Marcella Devoto4,6,7,10, Eric R. Rappaport1,4, Hakon Hakonarson3,4,6 & John M. Maris1,4,5
1 Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia,
2 Genomics and Computational Biology, University of Pennsylvania School of Medicine,
3 The Center for Applied Genomics, Children's Hospital of Philadelphia,
4 Department of Pediatrics, University of Pennsylvania School of Medicine,
5 Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine,
6 Division of Genetics, The Children's Hospital of Philadelphia,
7 Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104, USA
8 Department of Statistics, University of Florida and Children's Oncology Group, Gainesville, Florida, 32611, USA
9 Genomic Medicine, Imperial College London, London, SW7 2AZ, UK
10 University of Rome "La Sapienza", Department of Experimental Medicine, Rome, 00185, Italy
Common copy number variations (CNVs) represent a significant source of genetic diversity, yet their influence on phenotypic variability, including disease susceptibility, remains poorly understood. To address this problem in human cancer, we 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 susceptibility1, 2. We first genotyped 846 Caucasian neuroblastoma patients and 803 healthy Caucasian controls at 550,000 single nucleotide polymorphisms, and performed a CNV-based test for association. We then replicated significant observations in two independent sample sets comprised of a total of 595 cases and 3,357 controls. Here we describe the identification of a common CNV at chromosome 1q21.1 associated with neuroblastoma in the discovery set, which was confirmed in both replication sets. This CNV was validated by quantitative polymerase chain reaction, fluorescent in situ hybridization and analysis of matched tumour specimens, and was shown to be heritable in an independent set of 713 cancer-free parent–offspring trios. We identified a previously unknown transcript within the CNV that showed high sequence similarity to several neuroblastoma breakpoint family (NBPF) genes3, 4 and represents 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. These data demonstrate that inherited copy number variation at 1q21.1 is associated with neuroblastoma and implicate a previously unknown neuroblastoma breakpoint family gene in early tumorigenesis of this childhood cancer.
