食管癌中候选抑癌基因ING1突变的研究

Genetic alternations of candidate tumor suppressor ING1 gene in esophageal squamous cell cancer

目的 探讨候选抑癌基因ING1在食管癌发生、发展的作用。方法 用逆转录PCR (RT PCR)和免疫组织化学技术分别检测 3 1例食管鳞状细胞癌 (ESCC)中ING1mRNA和蛋白的表达情况 ;直接测序法检测RT PCR产物的基因变异 ;将染色体 13 q末端的微卫星位点作杂合性缺失 (LOH)分析。 结果 ( 1)几乎所有的肿瘤组织和相应的正常组织都有ING1mRNA表达 ,肿瘤组织中 ,一些表达ING1a少些 ,一些表达ING1b少些 ,但两亚型之间没有明显差别。( 2 )ING1蛋白的表达在肿瘤组织中均为阴性 ,而相应的正常组织中均为阳性。 ( 3 )在 3 1例中发现 4例为体细胞错义突变 ,2例为隐匿突变。 ( 4 ) 3 1例中有 17例 ( 5 5 % )出现LOH ,每一个位置的LOH的发生频率 >3 9%。结论 食管癌中ING1基因的突变和杂合性缺失可能影响它的转录和表达 ,它的表达减少与食管癌的发生、发展有关。

Objective To explore the effect of candidate tumor suppressor gene ING1 on the gensis and hrogression of esophageal squamous cell carcinoma (ESCC). Methods ING1 mRNA and protein in tumor tissues and matched normal tissues were monitored by RT-PCR and immunohistochemistry (IHC), respectively. Mutation analysis was detected by direct sequencing RT-PCR products. LOH analysis was tested by using microsatellite markers.Results (1) Almost all of the cancers and their normal counterparts expresed both ING1a and ING1b. Some tumors expresed less ING1a, and some tumors express less ING1b, but there were no obvious differences between the subtype and expression levels. (2) ING1 protein expression in matched normal tissues was positive weekly, and absent in all tumor tissues. (3) Four somatic missense mutations and two somatic silent mutations were detected in 31 ESCC patients. (4) Overall, LOH on 13q33-34 were observed in 17 of 31 patients (55%). The frequency of LOH for each of the loci was >39%.Conclusion The mutation and LOH of ING1 gene in ESCC maybe affect its transcription and expression. Decreased expression of ING1 gene relates with the genesis and progression of ESCC.