A nonredundant multicolor bar code as a screening tool for rearrangements in neoplasia.

Abstract

A chromosome bar code describes the colored pattern of chromosome segments and is derived by multicolor fluorescence in situ hybridization (FISH) of defined molecular probes. Published approaches to the simultaneous differentiation of whole karyotypes with bar codes have not allowed the unequivocal identification of all chromosome segments because of color redundancy of the patterns from a multitude of identically colored segments. Here, we present a chromosome bar code approach in which the problem of color redundancy has been overcome. It allows the detailed description of translocations, including breakpoints as well as intrachromosomal rearrangements in the karyotype of tumor cells. The resolution of discernable bars was increased to 100 bars per haploid chromosome set by including human chromosome-specific probes and more well-defined subregional probes such as chromosome arm- and segment-specific probes. Technically, no limitation to further increase in the resolution of the pattern became apparent. The approach was validated by the analysis of four established tumor cell lines widely used as models in cell biology, revealing numerous inter- and intrachromosomal rearrangements. Chromosome bar coding as presented here may provide further useful information for the subregional assignment of chromosomal breakpoints in complex chromosome aberrations, as found in various neoplasms that cannot be obtained by chromosome painting or classical banding techniques alone.