摘要
目的 观察散发性大肠癌 p5 3突变及其与微卫星不稳定 (MI) /复制差错 (RER)的相关性。方法 选择BAT 2 6 ,D2S119、D2S12 3、D3S12 93、D8S2 82、D13S16 0和D18S5 8等 7个微卫星位点 ,采用PCR银染法或ABI373自动序列分析仪检测MI/RER ;自动序列分析仪直接测序确立p5 3基因外显子 (E) 5 8突变 ;免疫组织化学法测定P5 3蛋白表达。结果 5 5例散发性结直肠癌中 ,P5 3E5 8突变率为 38 2 % (2 1/5 5 ) ,蛋白阳性表达率 6 0 % (33/5 5 ) ,两者符合率 4 2 %。MI阳性率为 2 7 2 %(15 /5 5 ) ,RER为 14 5 % (8/5 5 )。MI/RER阳性肿瘤较阴性者 p5 3基因总突变率和点突变率高 (MI组分别为 5 3 3%对 32 5 %和 5 3 3%对 30 % ;RER组为 6 2 5 %对 34%和 6 2 5 %对 30 2 % ,均P >0 0 5 ) ;但P5 3蛋白表达率则低 (MI组为 4 6 7%对 6 5 % ;RER组为 5 0 %对 6 2 % ,均P >0 0 5 ) ;而错义突变率和突变在CpG位点分布未见差异 (40 %对 30 %和 2 0 %对 12 5 % ,均P >0 0 5 ) ;另不同(CA)n位点MI对p5 3突变 /表达无明显影响。结论 MI/RER对p5 3E5 8突变无明显影响 ,MI/RER +肿瘤 p5 3突变倾向于高发 ,蛋白表达则呈低发 ,而错义突变率和突变在CpG位点的分布则相似。
Objective To study p53 muation and its association with microsatellite instability (MI) / replication error (RER) in sporadic colorectal cancer. Methods Fifty five cases of sporadic colorectal cancer were analyzed for MI/RER by PCR-based silver staining or ABI377 sequencer at following seven separate microsatellite loci: BAT-26,D2S119, D2S123, D3S1293, D8S282, D13S160 and D18S58. p53 mutations at exon 5-8 were detected by direct sequencing and its overexpressions performed by immunohistochemistry. Results p53 gene mutations were present in 38.2%(21/55) of the tumors and its overexpressions in 60 %(33/55)with a concordance rate of 42%. MI or RER positive rate was 27.2%(15/55) or 14.5%(8/55). MI/RER + cancers showed a tendancy of relatively high p53 total mutation and point mutation rates with 53.3% VS 32.5% and 53.3% VS 30% in MI group ( P >0.05)and with 62.5% VS 34% and 62.5% VS 30.2%( P >0.05) in RER group respectively;but they had low protein expression rate with 46.7% VS 65% in MI group and 50% VS 62% in RER group( P >0.05). There were no differences in p53 missense mutation rates and distributions at CpG sites with 40% VS 30% and 20% VS 12.5%( P >0.05) between the two kinds of MI/RER tumors.Furthermore, each (CA)n microsatellite locus had no significant effect on p53 mutation. Conclusion No significantrelationship is found between MI/RER and p53 mutation/overexpression in sporadic colorectal cancer.But MI/RER tumor tends to have relatively high p53 mutation and low overexpression rates.In addition,there exist no differences in p53 missense mutation rates and distributions at CpG sites between the two kinds of MI/RER tumors.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2003年第13期1130-1133,共4页
National Medical Journal of China
基金
国家自然科学基金资助项目 (3 960 0 0 5 5 )
教育部出国留学人员启动基金资助项目
浙江省教育厅课题基金资助项目
关键词
散发性大肠癌
P53基因
突变
微卫星不稳定
Sporadic colorectal cancer
Microsatellite instability
p53 gene
Mutation
