Chromosome bands 1p35-36 contain two distinct neuroblastoma tumor suppressor loci, one of which is imprinted.
A previous loss of heterozygosity (LOH) study of a series of 91 neuroblastomas suggested that the 1p35-36 region encodes at least two tumor suppressor genes (TSGs) of importance in neuroblastoma development. Here we present the results of a study including 205 neuroblastomas that were analyzed for LOH at chromosome 1 and MYCN amplification. The results corroborate the existence of two TSGs on 1p. Distinct 1p loci seem to be involved in MYCN single copy vs. MYCN amplified neuroblastoma, as these tumors display a different type of shortest region of overlap (SRO). About 15% of MYCN single copy neuroblastomas show 1p deletions of variable length with an SRO of 47 cR at 1p36.3. The lost alleles are preferentially of maternal origin (P = 0.0002), suggesting parental imprinting of the locus. MYCN amplified neuroblastomas have a contrasting pattern of 1p loss. These tumors display much larger deletions of at least 89 cR comprising the region from 1p36.1 to the telomere. LOH of 1p is detected in 86% of the cases. The lost alleles are of random parental origin, suggesting inactivation of a non-imprinted TSG.
Caron
H
H
Institute of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. H.N.Caron@AMC.UVA.NL
Spieker
N
N
Godfried
M
M
Veenstra
M
M
van Sluis
P
P
de Kraker
J
J
Voûte
P
P
Versteeg
R
R
D002871:Chromosome Banding; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D017353:Gene Deletion; D018628:Gene Dosage; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D009447:Neuroblastoma / Q000235:genetics*