遗传性非息肉病性结直肠癌错配修复基因MLH1启动子甲基化研究

Study of methylation of mismatch repair gene MLH1 in hereditary nonpolyposis colorectal cancer

目的了解中国人遗传性非息肉病性结直肠癌中MLH1基因启动子区CpG岛的过度甲基化现象。方法在错配修复基因微小突变检测和大片段缺失检测等实验的基础上,对47例DNA标本进行硫化处理,然后采用甲基化特异性PCR(MSP)方法检测标本中MLH1基因启动子的甲基化情况。结果47例标本中发现6例存在MLH1基因启动子过度甲基化,检出率为12.8%,其中4例表现为完全甲基化,2例表现为部分甲基化。结论MLH1基因启动子过度甲基化现象在遗传性非息肉病性结直肠癌中发生率较高,是HNPCC发病的相关因素之一。过度甲基化现象的研究有助于致癌机制的进一步探讨和揭示。

Objective To study CpG island hypermethylation of MLH1 promotor in hereditary nonpolyposis colorectal cancer. Method Forty-seven DNA examples were sulfurized, and then hypermethylation of MLH1 promotor was detected by methylation specific PCR, on the basis of detection of micromutation and large fragment deletion. Result In 47 examples,hypermethylation of MLH1 promoter was detected in 6 examples （ 12.8% ） , by analyzing the electropherogram of methylation specific PCR, 4 examples were completely methylated, and 2 examples were partly methylated. Conclusion Methylation of MLH1 promoter occurs rather frequently. And it might be one of the mechanisms in the development of hereditary nonpolyposis colorectal cancer. Methylation will help to reveal the mechanism of cancer-induced.