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

ABSTRACT

OBJECTIVE: We attempted to reveal the changes of the human telomerase reverse transcriptase (hTERT) alternative splicing pattern in gastric carcinogenesis. METHODS: Three alternative splicing sites (alpha, beta, gamma) were selected and designed PCR primer. The expression of 8 hTERT alternative splicing variants (ASVs) in normal gastric mucosa, precancerous lesions and gastric cancer were detected by seminested RT-PCR. The expression of beta-site remaining ASV (beta(+) ASV) in specimens of precancerous lesions and specimens of gastric cancer was detected by SYBER Green real-time PCR. RESULTS: The positive rate of alpha(+)beta(+)gamma(+) ASV 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 3 groups (p > 0.05). The positive rates of beta(+) ASVs (including alpha(+)beta(+)gamma(+) ASV, 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). SYBR Green real-time RT-PCR showed that the expression level of beta(+) ASV was 6.99 times higher in gastric cancer than in precancerous lesions. CONCLUSION: hTERT alternative splicing pattern is different during gastric carcinogenesis. beta(+) ASV was widely expressed in gastric carcinogenesis and may provide some information for diagnosis of gastric cancer or precancerous lesions.