Telomere erosion and numerical chromosomal instability in human cells undergoing immortalization

It has been a long-standing mystery why pre-immortal, immortalized and cancer cells universally have nonrandom numerical chromosome abnormalities. The objective of this study was to test whether telomere erosion induces numerical chromosome instability. Five human epithelial cells expressing human papillomavirus oncogenes, HPV16-E6 and E7, were used as cell models. Metaphase cells were collected for analyses of telomere profiles on individual chromosomes and numerical chromosome abnormalities in the entire process of immortalization. Quantitation of individual telomere signals were performed using combined quantitative telomere fluorescence in situ hybridization (Q-FISH) and Spectral Karyotyping (SKY). Our results showed persistent numerical chromosome instability, manifested as dynamic gains or losses of whole-chromosomes, in all the cell lines from pre-immortal stage to crisis. There was a general trend of dynamic increases in the frequencies of near-diploid (chromosome number = 40–47) or hypo-tetraploid (chromosome number = 81–91) cells, but near triploid and hyper-tetraploid cells were infrequently generated. However, there was no consistent relationship between the existence of the shortest telomeres and the frequencies of numerical abnormalities on individual chromosomes in the whole-genome of each analyzed cell line. Our data, therefore, indicate that telomere dysfunction does not seem to play a significant role in numerical chromosome instability in human cells undergoing immortalization. [This study was supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China, Project No. HKU 7385/03M, and a HKU Small Project Grant (2005-06)