Interphase cytogenetics: analysis of numerical chromosome aberrations in isolated cells

Probes which recognize pericentromeric repetitive sequences can be used to determine numerical chromosome aberrations in interphase nuclei. Under appropriate stringency conditions, these probes decorate only the chromosome from which they were derived. It has been assumed that abnormalities of signal number in interphase nuclei reflect aneuploidy rather than proliferation, but this has not been clearly demonstrated. In this paper, three alphoid probes (D3Z1, D11Z1, and DXZ1) were localized to the appropriate chromosomes and the factors governing the production of reproducible signal distributions from three aneuploid cervical carcinoma-derived epithelial cell lines were investigated. Abnormalities of signal number represent numerical chromosome aberrations rather than changes associated with proliferation. Using four simple rules of interpretation, reproducible results can be obtained with minimal technical variation and selection bias. These results demonstrate that pericentromeric repetitive probes can be used reproducibly to determine numerical chromosome aberrations independent of cell proliferation in interphase nuclei, a necessary prerequisite for the application of this approach to the analysis of human tumours.