Imbalance of morphologically addressed telophases reflects interphase DNA aneuploidy in tumorigenesis

Abstract

Chromosome division figures (CDFs) are quantitatively different from normal mitoses and represent a novel cytogenetic phenomenon. This investigation was focused on morphologically addressed bipolar telophases in histologically defined human biopsies and in the tumour breast cell-line MDA231. Single cell nuclei were recorded by image microphotometry on inflamed and premalignant lesions of skin (49 cases), oral mucosa (43) and colon mucosa (46). DNA content and replication status were analysed in interphase nuclei as well as in mitoses and in CDFs. In contrast to inflamed lesions, premalignancies were characterised by pronounced endoreplication, when the rate exceeding 5 c was > or = 10% in interphase nuclei. CDFs from the corresponding lesions showed an aberrant DNA content beyond 5 c even more frequently. DNA profiles of metaphases and telophases resembled those of prophases. Therefore, the DNA content of corresponding telophase hemispheres was measured. Severe differences averaged 0.3 c in MDA231 and up to 0.5 c in premalignant lesions. The mean difference between two corresponding hemispheres was 0.39 +/- 0.09 c in Bowenoid keratosis (n = 31), 0.40 +/- 0.08 c in high-grade dysplasia of oral mucosa (n = 16) and 0.21 +/- 0.03 c in high-grade dysplasia of colon adenoma (n = 65 telophases). As a control, the telophase difference was only 0.07 +/- 0.02 c (n = 23) in foetal liver and 0.06 +/- 0.01 c in 24 amnion cells. Thus, genomic instability and, in consequence, genomic imbalance can best be quantified from the DNA profiles of telophase CDFs and from the various DNA amounts in their hemispheres. A strong selection against telophases was observed in neoplasias developing DNA aneuploidy. Those aberrant telophases which escape selection are thought to enhance tumour progression.