子宫内膜癌中抑癌基因PTEN突变与微卫星不稳定性的相关性分析  

Correlation of PTEN Mutations with Microsatellite Instability in Endometrial Carcinoma

作　　者：赵岩[1] 刘岿然[1] 张淑兰[1] 

机构地区：[1]中国医科大学附属盛京医院妇产科,沈阳110004

出　　处：《中国医科大学学报》2010年第2期119-122,共4页Journal of China Medical University

基　　金：辽宁省教育厅青年基金资助项目(05L549)

摘　　要：目的探讨子宫内膜癌中抑癌基因PTEN突变和微卫星不稳定性(MSI)之间的关系,以及可能的发生机制。方法应用PCR方法检测实验组中5个微卫星位点的微卫星不稳定性;应用聚合酶链反应-单链构象多态性分析法(PCR-SSCP)和DNA序列分析法,检测40例子宫内膜癌和22例子宫内膜不典型增生、23例正常子宫内膜组织中PTEN第5、第8外显子突变情况,并进行突变测序。结果PTEN的突变在正常子宫内膜、子宫内膜不典型增生和子宫内膜癌中,表达差异有显著性(P<0.05);在子宫内膜不典型增生中,PTEN突变已经有了显著性的改变;PTEN基因突变与子宫内膜癌的手术病理分期有关(P<0.05);2例(2/11,18.2%)DNA测序发现PTEN突变发生在PTEN外显子8的poly(A)区域;子宫内膜癌中抑癌基因PTEN突变与微卫星不稳定性(MSI)高度相关(χ2=18.06,P<0.01)。结论PTEN突变和微卫星不稳定性是I型子宫内膜癌中重要的分子事件,二者在内膜癌中高度相关。可能存在由于MSI导致PTEN核苷酸重复序列突变增加的致癌途径。Objective To assess the prevalence and clinicopathologic significance of the microsatellite instability （MSI）,PTEN mutations and their correlations in endometrial carcinogenesis. Methods The MSI analysis was performed using five microsatellite markers in paired uterine endometrial carcinoma （UEC）and atypical endometrial hyperplasia （AH）. PTEN mutations were detected by single-strand conformation polymorphism（PCR-SSCP）analysis and DNA sequencing in UEC,AH and normal epithelimn （NE）. Rescults There was a significant difference in the incidence of FFEN mutations among AH,UEC and NE （P 〈 0.01 ）.PTEN mutations changed significantly in AH-the direct precursor to UEC （P 〈 0.01 ）. PTEN mutations correlated significantly with the clinical stage of the UEC （P 〈 0.05）. In UEC with MSI, PTEN mutations were detected in the short coding mononucleotide repeats（A）in 2 （ 18.2% ）of the 11 carcinomas.PTEN had a substantially higher frequency of mutations in UEC with MSI compared with the frequency of mutations in UEC without MSI （P 〈 0.05）. Conclusion PTEN mutations and MSI were two of the most common genetic alterations and correlated with each other in uterine endometrioid carcinoma. PTEN mutations might be secondary to deficiencies in mismatch repair and give some explanation for the frequent presence of PTEN mutations in MSI positive UEC.

关 键 词：子宫内膜肿瘤 子宫内膜不典型增生 PTEN 突变 DNA卫星 

分 类 号：R731.3[医药卫生—肿瘤]