Molecular Cytogenetic Analysis of Cervical Squamous Cell Carcinoma Cells Demonstrates Discordant Levels of Numerical and Structural Chromosomal Instability and Identifies ‘Selected’ Chromosome Rearrangements

Abstract

The processes underlying the karyotype complexity and heterogeneity characteristic of cervical squamous cell carcinoma (SCC) cells are not well understood, nor is it known which chromosome abnormalities provide a selective advantage. We used molecular cytogenetics to quantify for the first time the prevalence of all chromosomal abnormalities detectable in 8 cervical SCC cell lines. Of 225 rearrangements identified, 118 occurred frequently (≧70% metaphases) in one or more lines, indicating selection. Most of these selected rearrangements (107; 48% of the total) were included in published lists of abnormalities detected in independent cell stocks (although their significance was not previously recognised), indicating that they arose early in the establishment of the lines and were therefore most likely to have been present in the original tumours. The 8 cell lines showed 4.7- and 11.0-fold variation in levels of numerical and structural chromosomal instability (N-CIN and S-CIN) respectively, as determined by quantifying non-clonal abnormalities. We observed discordance between N-CIN and S-CIN (p = 0.148), with modal chromosome number showing a strong association with N-CIN (p = 0.007) but not with S-CIN (p = 0.602). These data imply that different mechanisms underlie N-CIN and S-CIN in cervical SCC. Despite ongoing S-CIN, newly arisen in vitro rearrangements were infrequently selected, supporting the view that selection is an important determinant of somatic evolution in malignancy. There was a positive association between numbers of non-clonal and clonal rearrangements (p = 0.002 for non-clonal vs. selected rearrangements), suggesting that factors affecting S-CIN determine the total numbers of rearrangements present in established cervical SCC cells.