Loss of heterozygosity for the short arm of chromosome 1 in human neuroblastomas: correlation with N-myc amplification.
Partial monosomy of the short arm of chromosome 1 is the most consistent cytogenetic abnormality found in human neuroblastomas, but its overall frequency and significance are unclear. Using a panel of chromosome-1-specific DNA probes that identify restriction fragment length polymorphisms, we demonstrate that 13 of 47 human neuroblastomas (28%) have somatic loss of heterozygosity (LOH) at one or more loci on the distal short arm of chromosome 1. the chromosomal region that shows LOH most consistently is between 1p36.1 and 1p36.3; loss of a gene or genes in this region may be critical for the development or progression of neuroblastomas. The region of LOH in human neuroblastoma may resemble that described for pheochromocytoma, medullary thyroid carcinoma, and melanoma, which are also tumors of neural-crest origin. Although LOH for distal chromosome 1p can occur in early stages of neuroblastoma, the loss usually occurs in tumors of advanced clinical stages. LOH for the short arm of chromosome 1 correlates significantly with N-myc amplification, suggesting that these two genetic events are related. Indeed, these two lesions appear to characterize a genetically distinct subset of particularly aggressive neuroblastomas.
Fong
C T
CT
Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO 63110.
Dracopoli
N C
NC
White
P S
PS
Merrill
P T
PT
Griffith
R C
RC
Housman
D E
DE
Brodeur
G M
GM
D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D015342:DNA Probes; D005784:Gene Amplification; D006579:Heterozygote; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc
D015342:DNA Probes; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc