Preferential amplification of the paternal allele in neuroblastomas with N-myc amplification.
There is increasing evidence that imprinting plays an important role in influencing the parental origin of genes involved in cancer-specific rearrangements. In advanced stage neuroblastomas, both allelic loss of the short arm of chromosome 1 (1p) and amplification of the proto-oncogene N-myc are often seen. Therefore, we analyzed 22 human neuroblastomas with N-myc amplification to determine the parental origin of the N-myc allele that is amplified and the 1p allele that is deleted. We used at least three polymorphisms for both the 1p and the N-myc locus to analyze blood and tumor samples from neuroblastoma patients, as well as blood samples from their parents. We determined that the paternal allele of N-myc was amplified in 12 of 15 informative cases (P = 0.02), and the paternal allele on 1p was lost in 6 of 11 informative cases (P > 0.2). These results suggest that parental imprinting does not appear to affect the 1p allele that is deleted, at least in the cases that we have examined. However, imprinting has an important influence on determining the N-myc allele that is amplified in these tumors, suggesting that the paternal allele is either more highly expressed or more likely to undergo amplification.
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
J M
JM
Cheng
J L
JL
Hiemstra
S S
SS
Schneider
B A
BA
Kaufman
A
A
Naumova
N K
NK
Cheung
S L
SL
Cohn
L
L
Diller
C
C
Sapienza
G M
GM
Brodeur
D000483:Alleles; D015139:Blotting, Southern; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc / Q000235:genetics*; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D009447:Neuroblastoma / Q000235:genetics*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D000090063:Proto-Oncogene Mas
D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas