Localization of a hereditary neuroblastoma predisposition gene to 16p12-p13

Background. Hereditary predisposition to develop neuroblastoma segregates a s an autosomal dominant Mendelian trait. Procedure. We have performed linka ge analysis on 10 families with neuroblastoma to localize a hereditary neur oblastoma predisposition gene (HNB1). Results. A single genomic interval at chromosome bands 16p12-p13 was consistent with linkage (lod = 3.46), and i dentification of informative recombinants defined a 25.9-cM critical region between D16S748 and D16S3068. Loss of heterozygosity was identified in 5/1 2 familial (42%) and 55/259 nonfamilial (21%) neuroblastomas at multiple 16 p polymorphic loci. A 12.8-cM smallest region of overlap of deletions was i dentified within the interval defined by linkage analysis (tel-D16S764-D16S 412-cen). Conclusions. Taken together, these data suggest that HNB1 is loca ted at 16p12-p13 and that inactivation of this gene may contribute to the p athogenesis of nonfamilial neuroblastomas. (C) 2000 Wiley-Liss, Inc.