Preliminary study on the alternative splicing pattern of human telomerase reverse transcriptase gene during gastric carcinogenesis

Objective: To investigate the changes of the human telomerase reverse transcriptase gene (hTERT) alterative splicing pattern in gastric carcinogenesis.

Methods: Three alternative splicing sites (alpha, beta, gamma) were selected to design primers. The expression of eight hTERT alternative splicing variants (ASVs) in normal gastric mucosa, precancerous lesions and gastric cancer was detected by semi-nested reverse transcription-polymerase chain reaction (RT-PCR). The expression of beta site-remaining ASV (beta (+) hTERT mRNA) in precancerous lesions and gastric cancer tissues was detected by SYBR green real-time RT-PCR.

Results: The positive rate of alpha(+) beta(+)gamma(+) hTERT mRNA was significantly higher in gastric cancer than in precancerous lesions and normal mucosa (94.7% vs. 40.0% and 0, P<0.05). The positive rates of other ASVs were not different among the three groups. The positive rates of beta deletion ASV were 72.2% in normal mucosa, 95.0% in precancerous lesions and 100.0% in gastric cancer. The mRNA level of beta(+) hTERT was 5.49 folds higher in gastric cancer than in precancerous lesions.

Conclusions: The hTERT alternative splicing pattern changes during gastric carcinogenesis. The beta(+) hTERT mRNA is expressed increasingly during gastric carcinogenesis and may provide useful information for diagnosis of gastric cancer or precancerous lesions.