摘要
目的 探讨微卫星不稳定性 (microsatelliteinstability ,MSI)在肾细胞癌中的表现及与基因突变的关系。方法 用PCR方法分析 34例肾细胞癌MSI表现 ;应用RT PCR方法检测 5种人类错配修复 (mismatchrepair,MMR)基因在肾细胞癌和肾癌细胞系mRNA转录水平的表达 ;用PCR SSCP技术对 15例肾细胞癌标本进行MMR基因hMLH1的 19个外显子进行筛选 ,观察基因突变的情况 ;用PCR方法检查肾癌组织中TGF βII型受体 (TGF βRII)基因和BAX基因移码突变的情况。 结果 34例肾细胞癌中有 15例 (4 4 1% )表现为MSI,并多见于晚期肿瘤 ;15例表达MSI阳性肾癌标本中 ,3例hMLH1基因mRNA表达缺失 ,3例表达明显降低 ,但在正常对照及PCC949细胞系都表达 5种MMR基因 ;PCR SSCP筛检结果 ,15例MSI(+ )细胞中 3例显示异常电泳带型 ;40 % (6 / 15 )及 2 7% (4 / 15 )分别见TGF βRII基因及BAX基因移码突变 ,但不表现在MSI(- )肾肿瘤及正常细胞中。 结论 肾细胞癌MSI与MMR基因表达有关 ,较高的突变率在肿瘤发生中的作用与MSI有关。
Objective To study the expression of microsatellite instability (MSI) in renal cell carcinoma (RCC) and its relationship with gene mutation. Methods Tumor samples from 34 patients with RCC were analyzed for MSI by PCR. RT PCR was used to evaluate the expression of mRNA of 5 human mismatch repair (MMR) genes in RCC and RCC cell lines. Mutation of hMLH1 gene coding regions was detected by PCR SSCP. PCR was used to check the mutations of TGF β?R?II gene and BAX gene in 15 MSI positive samples of RCC.[WT5”HZ]Results[WT5”BZ] Microsatellite changes were detected in 15 of 34 patients with RCC (44 1%). It might be associated with the progression of this disease. There were 3 of 15 MSI positive RCC cases without expression of MMR gene hMLH1, and in 3 of 15 cases its expression was decreased. All 5 MMR genes were expressed in normal and RCC 949 cell line. There were three mutations in 15 MSI positive cases. Frame shift mutation of TGF β?R?II gene and BAX gene was found in 6 and 4 of the 15 cases with MSI, respectively, but it was not found in MSI negative RCC and normal tissue. ConclusionMSI and expression of MMR genes are associated events in RCC. The effect of gene mutation on tumorgenerasis may be related to MSI.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2001年第1期11-13,共3页
Chinese Journal of Oncology
基金
卫生部基金!资助项目 (98 1 2 5 6 )
关键词
肾肿瘤
微卫星不稳定
基因突变
肾癌
Kidney neoplasms
Microsatellite instability
Gene mutation
