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 (α, β, γ) 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 β-site remaining ASV (β⁺ ASV) in specimens of precancerous lesions and specimens of gastric cancer was detected by SYBER Green real-time PCR. Results: The positive rate of α⁺β⁺γ⁺ 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 β⁺ ASVs (including α⁺β⁺γ⁺ ASV, α-deletion ASV, γ-deletion ASV, αγ-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 β⁺ ASV was 6.99 times higher in gastric cancer than in precancerous lesions. Conclusion: hTERT alternative splicing pattern is different during gastric carcinogenesis. β⁺ ASV was widely expressed in gastric carcinogenesis and may provide some information for diagnosis of gastric cancer or precancerous lesions.