Recurrent 1;17 translocations in human neuroblastoma reveal nonhomologous mitotic recombination during the S/G2 phase as a novel mechanism for loss of heterozygosity.
Neuroblastomas often show loss of heterozygosity of the chromosomal region 1p36 (LOH 1p), probably reflecting loss of a tumor-suppressor gene. Here we describe three neuroblastoma tumors and two cell lines in which LOH 1p results from an unbalanced translocation between the p arm of chromosome 1 and the q arm of chromosome 17. Southern blot and cytogenetic analyses show that in all cases the chromosome 17 homologue from which the 1;17 translocation was derived is still present and intact. This suggests a model in which a translocation between the short arm of chromosome 1 and the long arm of chromosome 17 takes place in the S/G2 phase of the cell cycle and results in LOH 1p. Nonhomologous mitotic recombination in the S/G2 phase is a novel mechanism of LOH.
Caron
H
H
Institute of Human Genetics, Emma Kinder Ziekenhuis, University of Amsterdam, The Netherlands.
van Sluis
P
P
van Roy
N
N
de Kraker
J
J
Speleman
F
F
Voûte
P A
PA
Westerveld
A
A
Slater
R
R
Versteeg
R
R
D000483:Alleles; D015139:Blotting, Southern; D002878:Chromosomes, Human, Pair 1; D002886:Chromosomes, Human, Pair 17; D016195:G2 Phase; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008938:Mitosis; D009447:Neuroblastoma / Q000235:genetics*; D016196:S Phase; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured