散发性结直肠癌中SMAD4基因的突变

Mutations of the SMAD4 gene in sporadic colorectal cancer

目的观察SMAD4基因在散发性结直肠癌中的突变,并探讨其对散发性结直肠癌发生发展的意义。方法对本院83例散发性结直肠癌患者,应用聚合酶链反应-单链构象多态性(PCR-SSCP)分析癌组织中SMAD4基因各外显子的突变情况,基因突变率与临床病理参数间采用x^2检验;应用多态性微卫星标记研究SMAD4基因所在18q21区的杂合性缺失。结果SMAD4基因在83例散发性结肠癌的患者中共有9例发生突变,平均突变率为10.8%。经x^2检验SMAD4基因突变率在肿瘤的Dukes分期及有无远处转移间差异有统计学意义(P<0.05),而与肿瘤的分化程度、发生部位及患者的性别差异无统计学意义(P>0.05)。18q21区的杂合性缺失率为62.71%,其中发生突变的9例均存在18q21区的杂合性缺失。结论SMAD4基因的突变可能介导了散发性结直肠癌后期的发生发展。

Objective To determine the mutations of the SMAD4 gene in sporadic colorectal cancer and discuss the significance in human colocrectal carcinogenesis. Methods Polymerase chain reaction-single-strand conformation polymorphism（PCR-SSCP） was applied to detect mutations of all exons of the SMAD4 gene in 83 cases of sporadic colorectal cancer. Χ^2 test was applied between the frequency of the mutation and the clinical characteristics of the colorectal cancer. Microsatellite markers were applied to study the loss of heterozygosity （LOH） of loci on 18q21, which contains the SMAD4 gene. Results The frequency of the SMAD4 mutation was 10.8% （9/83）. There were no significant among the differential grades, the location of the cancer and the sex of the cases on the rate of SMAD4 mutation （P 〉 0.05 ）. Among different Dukes stages,the rate of mutation of the SMAD4 gene in stage D was higher than in stage A,B,C （P 〈 0.05 ）. The frequency of mutation in cases with distant metastases was higher than in case with no distant metastases （P 〈0.01）. The rate of 18q21LOH was 62.71% and all tumors with SMAD4 gene mutation existed the 18q21LOH. Conclusion The later stage of carcinogenesis in sporadic colorectal cancer is probably mediated by mutation of the SMAD4 gene.