CDKN2A位点p16<sup>INK4α</sup>、p14<sup>ARF</sup>基因变异与胃癌发生的关系

汤绍辉; 杨冬华; 罗和生; 于皆平; 舒建昌

文章摘要

汤绍辉,杨冬华,罗和生,于皆平,舒建昌.CDKN2A位点p16^INK4α、p14^ARF基因变异与胃癌发生的关系[J].中华流行病学杂志,2004,25(6):517-520,521

CDKN2A位点p16^INK4α、p14^ARF基因变异与胃癌发生的关系

Relationship between alterations of p16^INK4a and p14^ARF genes of CDKN2A locus and gastric carcinogenesis

收稿日期:2003-04-08 出版日期:2014-09-17

DOI：

中文关键词: 胃肿瘤基因

英文关键词: Gastric cancer Genes

基金项目:

作者	单位
汤绍辉	暨南大学附属第一医院消化科广州, 510630
杨冬华	暨南大学附属第一医院消化科广州, 510630
罗和生	武汉大学人民医院消化科
于皆平	武汉大学人民医院消化科
舒建昌	暨南大学附属第一医院消化科广州, 510630

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中文摘要:

目的探讨p16^INK4a和p14^ARF基因变异与胃癌发生的关系。方法应用聚合酶链反应（PCR）、PCR-单链构象多态性（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p16^INK4a和p14^ARF基因纯合性缺失、突变、CpG岛甲基化及mRNA表达状况。结果（1）胃癌组织p16^INK4a和p14^ARF基因总缺失率为35.4％（17/48）,癌旁组织均未见纯合性缺失。（2）31例无纯合性缺失的胃癌及癌旁组织均未见p16^INK4a和p14^ARF基因点突变。（3）胃癌组织p16^INK4a和p14^ARF基因总甲基化率为47.90％（23/48）,癌旁组织仅2例甲基化,两者差异有显著性（P<0.01）。（4）胃癌组织p16^INK4amRNA缺失率为47.9％（23/48）,其中E1α和E2共甲基化者p16^INK4amRNA缺失率（100％,6/6）明显高于其他类型甲基化者（11.8％,2/17）（P<0.01）;胃癌组织p14^ARFmRNA缺失率为45.8％（22/48）,其中E1β和E2共甲基化者p14^ARFmRNA缺失率（100％,3/3）明显高于其他类型甲基化者（15％,3/20）（P<0.05）。（5）低未分化癌组p16^INK4a和p14^ARFmRNA共同缺失率（36.7％,11/30）明显高于高中分化癌组（5.6％,1/18）（P<;0.05）。结论胃癌中p16^INK4a和p14^ARF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。

英文摘要:

Objective To investigate the relationship between alterations of p16^INK4a and P14^ARF genes and gastric carcinogenesis.Methods Tumors and gastric tissues neighboring carinoma from 48 patients with gastric cancer were studied. Homozygous deletion,mutation,methylation of the CpG islands,mRNA expression of p16^INK4a and p14^ARF genes were assessed by polymerase chain reaction(PCR),PCR-single strand conformation polymorphism(SSCP),PCR based methylation assay,and reverse transcription (RT)-PCR.Results (1)The overall homozygous deletion rate of p16^INK4a,and p14^AR was 35.4% (17/ 48),and no homozygous deletion was examined in all the gastric tissues neighboring tumor.(2)There was no pont mutation of p16^INK4a and p14^ARF in 31 gastric cancers without homozygous deletion and in the matched gastric tissues adjacent to tumor.(3)Methylation of the CpG islands of p16^INK4a and p14^ADF was detected in 47.9% (23/48) of gastric cancers,while methylation was observed only in 2 of 48 gastric tissues neighboring cancers with a significant difference (P0.01).(4) The rate of p16^INK4a mRNA loss was 47.9% (23/48) in gastric cancer,and the cases of comined methylation of exons 1α and 2 had a higher be rate (100%, 6/6) of p16^INK4a mRNA than those of methylation form the other exons(11.8%,2/17) (P0.01).The be rate of p14^ARF mRNA was 45.8%(22/48) in gastric cancer,and patients with combined methylation of exons 1β and 2 had a higher loss rate (100%,3/3) of p14^ARF mRNA than those of the methylation from the other exons (15%,3/20) (P0.05).(5)The combined loss of p16^INK4a and p14^ARF mRNAs was examined in 1(5.6%) of 18 cases of well and moderately-differentiated carcinomas,and 11 (36.7%) of 30 cases of poorly and not-differentiated carcinomas with significan difference(P0.05).Conclusion p16^INK4a and p14^ARF genes were frequently inactivated by homozygous deletion and methylation of the 5' CpG islands in gastric cancer,which might have played an important role in the development of gastric cancer.

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