散发性结直肠癌微卫星不稳定性与hMSH3和hMSH6基因突变的研究

Microsatellite instability and mutation of DNA mismatch repair gene hMSH3 and hMSH6 in sporadic colorectal cancer

目的 探讨散发性结肠癌中微卫星不稳定性及其与错配修复基因hMSh 3和hMSh 6的关系。方法 应用放射性同位素为基础的聚合酶链式反应 (PCR)技术检测了 48例散发性结直肠癌中 4个位点 (D 2S 1 2 3、BAT -2 6、D 1 7S2 61、D 1 7S 799)的微卫星不稳定性和错配修复基因hMSh3和hMSh6的突变。结果 (1 )散发性结直肠癌的hMSh 3、hMSh6基因突变率分别为 :1 0 .4%、2 5 % ;(2 )D 2S 1 2 3、BAT -2 6、D 1 7S 2 61、D 1 7S 7994个位点的不稳定性检出率分别为 1 2 .5 %、1 8.8%、1 0 .4%、8.3 % ;(3 )hMSh 3和hMSh 6基因突变和微卫星不稳定性相关显著 (P <0 .0 1 )。结论 (1 )错配修复基因突变引起微卫星不稳定性是散发性结肠癌发生的重要机制 ;(2 )部分微卫星不稳定性是由错配修复基因hMSh 3和hMSh 6突变引起 ,其余的微卫星不稳定性可能涉及到其它错配修复基因 ;(3 )可通过单独检测BAT -2 6微卫星位点的不稳定性来确定RER阳性 ,这在肿瘤的防治中将是一种更加简单、准确的分子手段而应用于临床。

Objective To investigate the relationshipo tetueen microsatellite instability(MSI) and mismatch gemes hmsh 3 and hMsh 6 in sporadic colorectal cancer.Methods MSI at the locis D 2 S 123,BAT-26,D 17 S 261 and D 17 S 799 and mutation of mismatch repair genes hMSH 3 and hMSH 6 were studied by radioactive polymerase chain reaction(PCR) in surgical specimens trom 48 patients with sporadic colorectal cancer(SRC).Results The mutation of hMSH 3 and hMSH 6 occurred in 10.4% and 25% of the 48 specimens,repectively.MSI at the loci D 2 S 123,BAT-26,D 17 S 261 and D 17 S 799 occurred in 12.5%,18.8%,10.4% and 8.3% of the SRC xpecimens,respectively.There was significant correlation of MSI with the mutation of hMSH 3 and hMSH 6(P<0.01)?Conclusions MSI caused by mutation of mismatch repair genes is an important factor in the development of SRC.Some of MSI are caused by the mutation of mismatch repair genes hMSH3 and hMSH 6.It is a simple and accurate molecular method to verify positive RER by allaying the MSI at the locus BAT-26.