Identification of recurrent chromosomal rearrangements and the unique relationship between low-level amplification and translocation in gliablastoma

To elucidate the structural abnormalities and the relationship between chro mosome structural disorders and DNA copy number aberrations in tumor cells, we applied the techniques of spectral karyotyping (SKY), comparative genom ic hybridization (CGH), and fluorescence in situ hybridization (FISH), usin g 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 det ected by these cytogenetic methods. In particular, cell lines U251, SNB-19, and U373-MG showed very similar karyotypes. It is also interesting that re gions of DNA amplification were found translocated and/or inserted at a hig h rate (91.7%). In all, there were 12 amplified loci in five of the nine ce ll lines. These amplified chromosomal bands were scattered on the chromosom es, including the normal chromosome. with one exception (7q32-qter in U373- MG). FISH with YAC clones mapping to these chromosomal regions as DNA probe s 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 transloc ation or insertion of the relevant chromosomal locus, These studies shed li ght on typical derivative chromosomes and the relationship between DNA ampl ification and chromosomal translocation in glioblastoma. (C) 2001 Wiley-Lis s, Inc.