title: Evidence for a hereditary neuroblastoma predisposition locus at chromosome 16p12-13.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of Pennsylvania School of Medicine and Children's Hospital of Philadelphia, Abramson Pediatric Research Center, Philadelphia, Pennsylvania 19104-4318, USA. maris@email.chop.edu
authors.forename: John M
authors.initials: JM
authors.lastname: Maris
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Weiss
authors.forename: Yael
authors.initials: Y
authors.lastname: Mosse
authors.forename: George
authors.initials: G
authors.lastname: Hii
authors.forename: Chun
authors.initials: C
authors.lastname: Guo
authors.forename: Peter S
authors.initials: PS
authors.lastname: White
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hogarty
authors.forename: Tamar
authors.initials: T
authors.lastname: Mirensky
authors.forename: Garrett M
authors.initials: GM
authors.lastname: Brodeur
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
authors.forename: Margrit
authors.initials: M
authors.lastname: Urbanek
authors.forename: Suzanne
authors.initials: S
authors.lastname: Shusterman
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009447:Neuroblastoma / Q000235:genetics*