错配修复、微卫星不稳定性与散发性结直肠癌

Expression of DNA mismatch repair genes and microsatellite instability on the sporadic colorectal cancer

目的 探讨DNA错配修复基因、微卫星不稳定性与散发性结直肠癌发生发展的关系。方法 采用放射性同位素为基础的聚合酶链式反应 (PCR)技术 ,对 4 8例散发性结直肠癌中错配修复基因和四个位点微卫星不稳定性进行了检测。结果 4 8例散发性结直肠癌中hmsh3、hmsh6基因突变率分别为 10 4 %和 2 5 % ,四个位点微卫星不稳定性阳性率分别为D2S12 3(12 5 % )、BAT 2 6 (18 8% )、D17S2 6 1(10 4 % )、D17S799(8 3% ) ,hmsh3、hmsh6基因突变和微卫星不稳定性多为分化不良的癌 ,多位于右半结肠 ,而与患者的性别、淋巴结转移、Ducks分期无关。结论 错配修复基因突变与微卫星不稳定性是散发性结直肠癌发生的早期分子事件 。

Objective To explore the relation between sporadic colorectal cancer(SRC) and microsatellite instability(MSI) caused by the mutation of the mismatch repair gene.Methods MSI at four loci and mutation of the mismatch repair gene were studied in 48 surgical specimens of sporadic colorectal cancer with polymerase chain reaction(PCR) based on radioactive isotope. Results The mutation of hMSH3, hMSH6 occurred in 10.4%, 25% of SRC and MSI at the loci D2S125,BAT 26,D17S261,D17S799 occurred in 12.5%,18.8%,10.4%,8.3% of the SRC.The incidence of MSI and mutation of hMSH3 and hMSH6 were siginficantly in right, poorly differentiated CRC.There was no siginificant correlation of MSI to the age, gender, lymphnode metastasis and Dukes stage.Conclusion MSI caused by mutation of mismatch repair gene is an early molecular marker of SRC and represents a new carcinogenic mechanism besides LOH.