Spectral karyotyping suggests additional subsets of colorectal cancers characterized by pattern of chromosome rearrangement

The abundant chromosome abnormalities in most carcinomas are probably a ref lection of genomic instability present in the tumor, so the pattern and var iability of chromosome abnormalities will reflect the mechanism of instabil ity combined with the effects of selection. Chromosome rearrangement was in vestigated in 17 colorectal carcinoma-derived cell lines. Comparative genom ic hybridization showed that the chromosome changes were representative of those found in primary tumors. Spectral karyotyping (SKY) showed that trans locations were very varied and mostly unbalanced, with no translocation occ urring in more than three lines. At least three karyotype patterns could be distinguished. Some lines had few chromosome abnormalities: they all showe d microsatellite instability, the replication error (RER)+ phenotype. Most lines had many chromosome abnormalities: at least seven showed a surprising ly consistent pattern, characterized by multiple unbalanced translocations and intermetaphase variation, with chromosome numbers around triploid, 6-16 structural aberrations, and similarities in gains and losses. Almost all o f these were RER-, but one, LS411, was RER+. The line HCA7 showed a novel p attern, suggesting a third kind of genomic instability: multiple reciprocal translocations, with little numerical change or variability. This line was also RER+. The coexistence in one tumor of two kinds of genomic instabilit y is to be expected if the underlying defects are selected far in tumor evo lution.