Evidence for a hereditary neuroblastoma predisposition locus at chromosome 16p12-13.
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.
Maris
John M
JM
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
Weiss
Matthew J
MJ
Mosse
Yael
Y
Hii
George
G
Guo
Chun
C
White
Peter S
PS
Hogarty
Michael D
MD
Mirensky
Tamar
T
Brodeur
Garrett M
GM
Rebbeck
Timothy R
TR
Urbanek
Margrit
M
Shusterman
Suzanne
S
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*