Chromosomal instability and cytoskeletal defects in oral cancer cells

Oral squamous cell carcinomas are characterized by complex, often near-trip loid karyotypes with structural and numerical variations superimposed on th e initial clonal chromosomal alterations. We used immunohistochemistry comb ined with classical cytogenetic analysis and spectral karyotyping to invest igate the chromosomal segregation defects in cultured oral squamous cell ca rcinoma cells. During division, these cells frequently exhibit lagging chro mosomes at both metaphase and anaphase, suggesting defects in the mitotic a pparatus or kinetochore. Dicentric anaphase chromatin bridges and structura lly altered chromosomes with consistent long arms and variable short arms, as well as the presence of gene amplification, suggested the occurrence of breakage-fusion-bridge cycles. Some anaphase bridges were observed to persi st into telophase, resulting in chromosomal exclusion from the reforming nu cleus and micronucleus formation. Multipolar spindles were found to various degrees in the oral squamous cell carcinoma lines. In the multipolar spind les, the poles demonstrated different levels of chromosomal capture and ali gnment, indicating functional differences between the poles. Some spindle p oles showed premature splitting of centrosomal material, a precursor to ful l separation of the microtubule organizing centers. These results indicate that some of the chromosomal instability observed within these cancer cells might be the result of cytoskeletal defects and breakage-fusion-bridge cyc les.