The relationship between spontaneous telomere loss and chromosome instability in a human turner cell line

Chromosome instability plays an important role in cancer by promoting the a lterations in the genome required for tumor cell progression. The loss of t elomeres that protect the ends of chromosomes and prevent chromosome fusion has been proposed as one mechanism for chromosome instability in cancer ce lls, however, there is little direct evidence to support this hypothesis. T o investigate the relationship between spontaneous telomere loss and chromo some instability in human cancer cells, clones of the EJ-30 tumor cell line were isolated in which a herpes simplex virus thymidine kinase (HSV-tk) ge ne was integrated immediately adjacent to a telomere, Selection for HSV-tk- deficient cells with ganciclovir demonstrated a high rate of loss of the en d these marked" chromosomes (10(-4) events/cell per generation). DNA sequen ce and cytogenetic analysis suggests that the loss of function of the HSV-t k gene most often involves telomere loss, sister chromatid fusion, and prol onged periods of chromosome instability. In some HSV-tk-deficient cells, te lomeric repeat sequences were added on to the end of the truncated HSV-tk g ene at a new location, whereas in others, no telomere was detected on the e nd of the marked chromosome. These results suggest that spontaneous telomer e loss is a mechanism for chromosome instability in human cancer cells.