Identification of recurrent chromosomal rearrangements and the unique relationship between low-level amplification and translocation in glioblastoma.
To elucidate the structural abnormalities and the relationship between chromosome structural disorders and DNA copy number aberrations in tumor cells, we applied the techniques of spectral karyotyping (SKY), comparative genomic hybridization (CGH), and fluorescence in situ hybridization (FISH), using yeast artificial chromosome (YAC) probes for nine human glioblastoma cell lines. One striking finding was that independently derived cell lines had the same recurrent marker chromosomes. Seven recurrent chromosomes were detected by these cytogenetic methods. In particular, cell lines U251, SNB-19, and U373-MG showed very similar karyotypes. It is also interesting that regions of DNA amplification were found translocated and/or inserted at a high rate (91.7%). In all, there were 12 amplified loci in five of the nine cell lines. These amplified chromosomal bands were scattered on the chromosomes, including the normal chromosome, with one exception (7q32-qter in U373-MG). FISH with YAC clones mapping to these chromosomal regions as DNA probes often showed DNA probe signals not only at original chromosomal sites but also in translocated or inserted segments. This form of DNA amplification was characterized by low-level increases (four- to 10-fold) and by translocation or insertion of the relevant chromosomal locus. These studies shed light on typical derivative chromosomes and the relationship between DNA amplification and chromosomal translocation in glioblastoma.
Kubota
H
H
Department of Pathology, Yamaguchi University School of Medicine, Yamaguchi, Japan.
Nishizaki
T
T
Harada
K
K
Harada
K
K
Oga
A
A
Ito
H
H
Suzuki
M
M
Sasaki
K
K
D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D005784:Gene Amplification / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D014178:Translocation, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured