食管鳞癌MLH1基因改变及其与微卫星不稳定的关系(英文)

Alterations of MLH1 and Microsatellite Instability in Esophageal Squamous Cell Carcinomas

MLH1是位于3p21.3上的一个DNA错配修复基因,其异常与多种肿瘤相关。为探索食管鳞癌中MLH1 基因改变及其与微卫星不稳定(MSI)的关联情况,采用微卫星分析和RT PCR方法检测了14个微卫星标志在食 管癌中的状况及MLH1转录水平的表达,发现35%的食管癌出现至少一个微卫星的不稳定,66.7%的肿瘤在 MLH1基因内标志D3S1611位点表现为杂合性丢失,但是MLH1没有明显的mRNA表达下调。MSI与食管癌分 期、分级、淋巴结转移、患者年龄和性别等参数及MLH1基因杂合性丢失(LOH)之间无统计学意义的相关性。这些 结果表明:食管癌中MLH1存在较高频率的等位基因丢失,但其mRNA表达水平并无明显异常;所测微卫星标志 的不稳定是食管癌的频发事件,与MLH1基因LOH不存在必然联系。

Human MLH1 is one of the DNA mismatch repair genes and located in chromosome 3p21.3.Alterations of the MLH1 were associated with various kinds of human tumors.The present study was to investigate (allelic) loss of MLH1 and microsatellite instability (MSI) in esophageal squamous cell carcinomas (ESCC),and to estimate the correlation between MSI status and allelic loss of the MLH1 gene.The MSI of 14 microsatellite markers and mRNA expression of MLH1 were assessed in a large cohort of patients with ESCC by using denaturing polyacrylamide gel electrophoresis (PAGE) and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques.Thirty-five percent of tumors displayed MSI in at least one tested marker.MSI in D3S1611,an intragenic marker of the MLH1,was observed in 66.7% of tumors.No down-expression of MLH1 was found at the transcriptional level.The presence of MSI did not correlate with tumor stage,degree of differentiation,lymphonode-metastasis,age and sex of the patients,neither with allelic loss of the MLH1 gene.The data suggested that LOH of MLH1 is common in ESCC,but not lead to the alteration of MLH1 at the level of RNA expression.MSI in tested microsatellite markers occurs frequently in ESCC but is not associated with allelic loss of the MLH1 gene.