Centrosome amplification and instability occurs exclusively in aneuploid, but not in diploid colorectal cancer cell lines, and correlates with numerical chromosomal aberrations

Measurement of the nuclear DNA content allows classification of human cance rs as either diploid or aneuploid. To gain further insight into mechanisms of aneuploidy, we compared the cytogenetic profile of mismatch-repair-defic ient diploid versus mismatch-repair-proficient aneuploid colorectal carcino ma cell lines using comparative genomic hybridization and spectral karyotyp ing. Aneuploid carcinomas revealed an average of 19 chromosomal imbalances per cell line. Such numerical aberrations were exceedingly scarce in the di ploid tumors. This pattern of chromosomal aberrations is consistent with a mechanism involving the impairment of chromosome segregation fidelity durin g mitotic cell division. In support of this idea, we demonstrate the exclus ive occurrence of centrosome amplification and instability in all of the an euploid tumor cell lines analyzed. All diploid tumors contained centrosomes that were functionally and structurally indistinguishable from those in no rmal human fibroblasts. Due to the observed differences in centrosomes betw een these two classes of tumors, we incubated the cells with the microtubul e depolymerizing drugs nocodazole and griseofulvin. Our results indicate th at the aneuploid tumor cell lines have an increased sensitivity to these re agents and a delay in aster formation and microtubule regrowth. However, mi crotubule nucleation was initiated from one or two centers in both the dipl oid and aneuploid cells. These observations support the notion that the int egrity of the centrosome plays a central role in the development of aneuplo idy. Genes Chromosomes Cancer 27: 183-190, 2000. Published 2000 Wiley-Liss, Inc.dagger.