[Changes of alternative splicing variants of human telomerase reverse transcriptase during gastric carcinogenesis].

Background & Objective: The expression of human telomerase reverse transcriptase (hTERT) is positively correlated to the activity of telomerase. Alternative splicing exists in the transcription of hTERT and special splicing patterns may change during tumor progression. This study was to reveal the changes of 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 18 specimens of normal gastric mucosa, 20 specimens of precancerous lesions and 19 specimens of 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 positive rates of beta+ hTERT mRNA (including alpha+beta+gamma+ hTERT mRNA, alpha-deletion ASV, gamma-deletion ASV, alphagamma-deletion ASV) were 11.1% in normal mucosa, 40.0% in precancerous lesions and 94.7% in gastric cancer (P<0.05). The mRNA level of beta+ hTERT was 6.99 times higher in gastric cancer than in precancerous lesions.

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