Telomerase reverse transcriptase gene amplification in hepatocellular carcinoma.

Abstract

Telomerase activation is essential for the immortality of cancer cells. The expression of telomerase reverse transcriptase (hTERT), the catalytic component of the telomerase complex, regulates telomerase activity in human cancers. Amplification of the hTERT gene, located at chromosome 5p, is thought to be a potential genetic event contributing to telomerase activation in sporadic tumors. The amplification of the hTERT gene was examined in 46 surgically resected hepatocellular carcinomas (HCC) by real-time polymerase chain reaction and the status was compared with the expression of hTERT mRNA and clinicopathological parameters. Amplified hTERT genes were found in 21.7% (10/46) of HCC. The incidence of amplified hTERT genes in poorly differentiated HCC (6/12, 50%) was significantly higher than that in highly to moderately differentiated HCC (4/34, 11.8%; P = 0.012). Tumor size in those cases with hTERT gene amplification was larger compared to those cases with no amplification (P = 0.047). Amplification of the hTERT gene was not observed in non-cancerous tissues. The hTERT mRNA level did not correlate with the number of hTERT genes. Based on these results, it is thought that hTERT gene amplification is a cancer-specific event, and may furthermore contribute to the dedifferentiation and development of HCC. However, hTERT gene overexpression was rarely due to an increased hTERT gene copy number in HCC.