Decrease of telomeres and increase of interstitial telomeric sites in chromosomes of short-term cultured gastric
Kiyotaka Kashima1, Atsushi Nanashima, Toru Yasutake
1Division of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Background:
Deletion or shortening of chromosomal telomeres is associated with cellular aging and carcinogenesis. Telomeric sites are interstitially located in chromosomes. To clarify the frequency of telomerase abnormalities in cancer and their relationship with any characteristics of gastric carcinomas, telomeric aberrations in eleven cultured specimens of human gastric cancer were investigated by cytogenetic analysis.
Materials And Methods:
Chromosomal metaphase specimens, obtained by primary culture of cells from surgical specimens of eleven gastric cancer patients, were examined by fluorescent in situ hybridization (FISH) using all telomeric and chromosome 17 specific-telomeric DNA probes. The number of telomeric signals and interstitial telomeric signals (ITS) were counted. DNA ploidy was examined by flow cytometry.
Results:
The mean telomere signal per nucleus (MTS) observed in peripheral blood lymphocytes (PBLs) of normal volunteers (n=10) was 71.3+/-3.9%. The MTS in the carcinoma cells (46.9+/-2.6%) was significantly lower than in PBLs (p<0.01). Although ITS were not observed in PBLs, the mean rate of ITS was 41.2+/-22.0%, and the mean rate of ITS per chromosome was 2.1+/-2.1% in the cancer specimens. In DNA aneuploid carcinoma cells, the MTS was significantly lower, the mean rate of ITS tended to be higher (p=0.072), and the mean rate of ITS per chromosome was significantly higher (p<0.05), than in DNA diploid lymphocytes. Histologically, the mean rate of ITS per chromosome in carcinomas with venous infiltrations was significantly greater than in those without (p<0.05).
Conclusion:
Deletion and interstitial translocation of telomeric loci of chromosomes were frequent alterations in gastric carcinoma cells and increased numbers of interstitial telomeric signals were associated with venous invasion.
