【摘要】 目的 :探讨胃癌组织p14ARF基因变异及其意义。方法 :应用PCR、PCR -SSCP、PCR甲基化分析法和RT -PCR分别检测 48例胃癌及癌旁组织中p14ARF基因纯合性缺失、突变、CpG岛甲基化及其mRNA表达状况。结果 :①胃癌组织p14ARF基因纯合性缺失率为 3 1 3 % (15 / 48) ,癌旁组织均未见纯合性缺失。② 3 3例无纯合性缺失的胃癌及癌旁组织均未见p14ARF基因点突变。③胃癌组织p14ARF基因甲基化率为 47 9% (2 3 / 48) ,癌旁组织仅 2例甲基化 ,两者差异有显著 (P <0 0 1)。④ 45 8% (2 2 / 48)的胃癌组织p14ARFmRNA无表达。 3例外显子E1β和E2共甲基化者p14ARFmRNA均无表达 (10 0 % ) ,2 0例单纯E2甲基化者仅 3例无表达 (15 % ) ,两者差异有显著 (P <0 0 5 )。结论 :胃癌中p14ARF基因失活多由纯合性缺失和 5’CpG岛甲基化所致 ,其表达缺失与胃癌的发生密切相关更多还原

【Abstract】 AIM: To investigate the significance and changes of p14 ARF gene in gastric cancer.METHODS: The tumors and gastric tissues neighboring carcinoma from 48 patients with gastric cancer were studied. The homozygous deletions, mutations, methylation of the CpG islands, and mRNA expression of p14 ARF gene were assessed by PCR, PCR-SSCP, PCR based methylation assay, and RT-PCR.RESULTS: ①The homozygous deletion rate of p14 ARF was 31 3% (15/48), and no homozygous deletions were examined in all the gastric tissues neighboring tumor. ②There were no point mutations of p14 ARF in 33 gastric cancers without homozygous deletion and in the matched gastric tissues adjacent to tumor. ③Methylation rate of the CpG islands of p14 ARF was significantly higher in gastric cancers(47.9%, 23/48) than that in gastric tissues neighboring cancer (4.2%, 2/48)( P<0.01 ).④ No expression of p14 ARF mRNA was detected in 45.8%(22/48) of gastric cancers. Moreover, the negative rate (100%, 3/3) of p14 ARF mRNA of gastric cancers with the combined methylation of exons 1β and 2 was significantly higher than that (15%, 3/20) of the sole methylation of exon2( P<0.05 ). CONCLUSION: p14 ARF gene is frequently inactivated by homozygous deletion and methylation of the 5’ CpG islands in gastric cancer, which may play an important role in the development of gastric cancer.更多还原