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目的探讨脆性组氨酸三联体(FHIT)基因和Ras相关结构域家族1A基因(RASSF1A)基因杂合性丢失(loss of heterozygosity,LOH)在宫颈癌发生发展中的作用。方法选取FHIT基因的2个位点D3S1234和D3S4103及RASSF1A基因的2个位点D3S1478和D3S4604,采用聚合酶链反应(PCR)法及垂直电泳技术,对50例宫颈癌及40例宫颈上皮内瘤样病变(Cervical Intraepithelial Neoplasia,CIN)组织进行杂合性丢失检测。结果 FHIT基因中,在D3S1234位点上CINⅠ-Ⅱ和CINⅢ的LOH发生频率分别为32.0%、66.7%,在D3S4103位点上CINⅠ-Ⅱ和CINⅢ的LOH阳性率分别为24.0%、60.0%,随CIN级别的增加LOH阳性率呈逐渐递增趋势(P<0.05);在D3S1478位点上CINⅠ-Ⅱ和CINⅢ的LOH阳性率分别为12.0%、53.3%,在D3S4604位点上CINⅠ-Ⅱ和CINⅢ的LOH阳性率分别为24.0%、60.0%,随CIN级别的增加LOH阳性率呈逐渐递增趋势CIN(P<0.05)。结论 FHIT基因和RASSF1A基因的LOH可能是宫颈癌发生过程中的较晚期事件。
Objective To investigate the role of fragile histidine triad (FHIT) gene and loss of heterozygosity (LOH) of Ras-related gene family 1A gene (RASSF1A) gene in the development of cervical cancer. Methods The two sites D3S1234 and D3S4103 of FHIT gene and two sites of D3S4103 of RASSF1A gene were selected. PCR and vertical electrophoresis were used to detect the expression of three genes in 50 cases of cervical cancer and 40 cases of cervical intraepithelial neoplasia Cervical Intraepithelial Neoplasia (CIN) Tissue for loss of heterozygosity. Results The frequencies of LOH in CINⅠ-Ⅱ and CINⅢ at FISH were 32.0% and 66.7% respectively at D3S1234 loci, and positive rates of LOH at CINⅠ-Ⅱ and CINⅢ at D3S4103 were 24.0% and 60.0% respectively The positive rate of LOH increased gradually with the increase of CIN level (P <0.05). The positive rate of LOH at CINⅠ-Ⅱ and CINⅢ at D3S1478 was 12.0% and 53.3%, respectively. At D3S4604, CINⅠ-Ⅱ and CINⅢ The positive rate of LOH was 24.0% and 60.0%, respectively. The positive rate of LOH gradually increased with the increase of CIN level (P <0.05). Conclusions The LOH of FHIT gene and RASSF1A gene may be the later event in cervical carcinogenesis.