Maris John M, Weiss Matthew J, Mosse Yael, Hii George, Guo Chun, White Peter S, Hogarty Michael D, Mirensky Tamar, Brodeur Garrett M, Rebbeck Timothy R, Urbanek Margrit, Shusterman Suzanne
Department of Pediatrics, University of Pennsylvania School of Medicine and Children's Hospital of Philadelphia, Abramson Pediatric Research Center, Philadelphia, Pennsylvania 19104-4318, USA.
Cancer Res. 2002 Nov 15;62(22):6651-8.
Hereditary predisposition to develop neuroblastoma (Online Mendelian Inheritance in Man 256700), a pediatric cancer of the sympathetic nervous system, segregates as an autosomal dominant Mendelian trait. We performed linkage analysis on seven families with two or more first-degree relatives affected with neuroblastoma to localize a hereditary neuroblastoma predisposition gene. A single interval at chromosome bands 16p12-13 was the only genomic region consistent with linkage (LOD(MAX) = 3.30 at D16S764). Identification of informative recombination events in linked families defined a 28.0-cM region between D16S748 and D16S769 that cosegregated with the disease in each pedigree. Loss of heterozygosity was identified in 5 of 11 familial neuroblastomas and 68 of 336 nonfamilial neuroblastomas (20.2%) at multiple 16p polymorphic loci. A 14.5-cM smallest region of overlap of somatic deletions was identified within the interval defined by linkage analysis (tel-D16S500-D16S412-cen). Taken together, these data suggest that a hereditary neuroblastoma predisposition gene (HNB1) is located at 16p12-13 and that disruption of this gene may contribute to the pathogenesis of nonfamilial neuroblastomas.
患神经母细胞瘤（《人类孟德尔遗传在线》编号256700）的遗传易感性表现为一种常染色体显性孟德尔性状，神经母细胞瘤是一种小儿交感神经系统癌症。我们对7个有两个或更多患神经母细胞瘤的一级亲属的家庭进行了连锁分析，以定位遗传性神经母细胞瘤易感基因。16号染色体12 - 13带的一个单一区间是唯一与连锁一致的基因组区域（在D16S764处，最大对数优势比（LOD）= 3.30）。在连锁家庭中鉴定出信息性重组事件，确定了D16S748和D16S769之间一个28.0厘摩的区域，该区域在每个家系中都与疾病共分离。在11例家族性神经母细胞瘤中的5例以及336例非家族性神经母细胞瘤中的68例（20.2%）的多个16p多态性位点发现杂合性缺失。在连锁分析确定的区间（端粒 - D16S500 - D16S412 - 着丝粒）内鉴定出一个14.5厘摩的体细胞缺失最小重叠区域。综上所述，这些数据表明遗传性神经母细胞瘤易感基因（HNB1）位于16p12 - 13，该基因的破坏可能与非家族性神经母细胞瘤的发病机制有关。
