Evidence of chromosomal instability in prostate cancer determined by spectral karyotyping (SKY) and interphase FISH analysis

The way in which cytogenetic aberrations develop in prostate cancer (CaP) i s poorly understood. Spectral karyotype (SKY) analysis of Cap cell lines ha s shown that they have unstable karyotypes and also have features associate d with chromosomal instability (GIN), To accurately determine the incidence of de novo structural and numerical aberrations in vitro in CaP, we perfor med SKY analysis of three independent clones derived from one representativ e cell line, DU145, The frequent generation of new chromosomal rearrangemen ts and a wide variation in the number of structural aberrations within two to five passages suggested that this cell line exhibited some of the featur es associated with a CIN phenotype. To study numerical cell-to-cell variati on, chromosome 8 aneusomy was assessed in the LNCaP, DU145, and PC-3 cell l ines and a patient cohort of 15 GaP primary tumors by interphase fluorescen ce in situ hybridization (FISH). This analysis showed that a high frequency of numerical alteration affecting chromosome 8 was present in both in vitr o and in Cap tissues. In comparison to normal controls, the patient cohort had a statistically significant (P<.05), greater frequency of cells with on e and three centromere 8 copies. These data suggest that a GIN-like process may be contributing towards the generation of de novo numerical and struct ural chromosome abnormalities in CaP.