Telomere changes in human hepatocellular carcinomas and hepatitis virus infected noncancerous livers

Abstract

Telomeres, at the ends of eukaryotic chromosomes, are defined functionally as necessary for chromosome stability. Chromosome instability induced in part by loss of telomeric DNA has been considered to play a significant role in the development of human cancers. However, little is known about the status of telomeres per se during human hepatocellular carcinoma (HCC) development. The study was conducted to determine the length of terminal restriction fragments (TRFs) at the telomeric ends in 23 HCCs and 23 corresponding noncancerous liver tissues from the same patients harboring hepatitis virus infections, and in 5 samples of noncancerous livers without the hepatitis virus. The latter samples had been obtained as controls at surgery for metastatic liver tumors. All 23 HCCs demonstrated reduction in TRF length compared with the corresponding noncancerous liver tissues with viral infection. The TRF in the latter cases also demonstrated a significant shortening as compared with the virus free control tissue, the degree being calculated to represent an average of 42 cell divisions. Reduction in TRF length in HCC samples tended to increase with the tumor diameter, although this failed to show statistical significance. These results indicate that telomere shortening occurs during HCC development. The fact that this change is already evident in noncancerous liver tissues from patients with viral hepatitis suggests that it may play an important role in the associated generation of tumors.