【摘要】 目的:探讨结直肠癌中APC、K-ras、p53基因突变模式。方法:应用酚/氯仿法提取48例结直肠癌组织及其相应正常黏膜组织的DNA,用聚合酶链反应(PCR)、单链构象多态性分析(SSCP)和DNA测序等方法检测APC基因第15外显子突变密集区(mutation cluster region,MCR)区段、K-ras和p53基因的突变。结果:APC、K-ras和p53基因的突变率分别为37.5%(18/48)、43.8%(21/48)和35.4%(17/48)。48例结直肠癌组织中,有42例发生APC、K-ras或p53基因突变,突变率高达87.5%(42/48),其中仅有APC、K-ras或p53 1种基因发生突变的发生率分别为16.7%(8/48)、25.0%(12/48)和20.8%(10/48)。单独1种基因发生突变的总发生率为62.5%(30/48)。APC和p53,APC和K-ras或p53和K-ras 2种基因均有突变的发生率分别为6.3%(3/48)、10.4%(5/48)和4.2%(2/48)。APC、K-ras和p53 3种基因均发生突变的发生率为4.2%(2/48)。2种和3种基因均发生突变的总发生率为25%(12/48)。结论:结直肠癌的发生、发展并不完全遵循由正常结直肠黏膜上皮细胞向腺瘤和侵袭性癌转化的过程中,及依次发生“APC→K-ras→p53→DCC”突变累积这一经典的结直肠癌发生发展模式,可能存在其他结直肠癌发病机制。更多还原

【Abstract】 Objective:To investigate the mutation pattern of adenomatous polyposis coli(APC),Kirsten-ras(K-ras) and p53 genes in sporadic colorectal cancer tissues.Methods:DNA was extracted by phenol-chloroform method from tumor and normal mucosal tissues of 48 patients with colorectal cancer.The mutations of the mutation cluster region(MCR) of the APC,K-ras,and p53 were analyzed using polymerase chain reaction(PCR),single-strand conformation polymorphism(SSCP) analysis,and DNA sequencing methods.Results:The mutations of APC,K-ras,and p53 was 37.5%(18/48),43.8%(21/48),and 35.4%(17/48),respectively.Forty two of 48 patients(87.5%) contained mutations in at least one of these genes including one gene mutation,two or three gene mutations.The rate of only one gene mutation of APC,K-ras,and p53 was 16.7%(8/48),25.0%(12/48),and 20.8%(10/48),respectively.The total rate of one gene mutation was 62.5%(30/48).The mutations in both APC and p53 was 6.25%(3/48),in both APC and K-ras was 10.42%(5/48),in both p53 and K-ras was 4.17%(2/48).Only 2 cases(4.17%) contained mutations in APC,K-ras,and p53.The total rate of combined mutation two or three genes was 25%.Conclusion:The combinations of mutations in two or three genes was uncommon.There might be an alternative mechanism during the carcinogenesis of sporadic colorectal cancers,in addition to the widely accepted genetic model that the sequential accumulation of mutations in specific genes,APC→K-ras→p53→DCC,drives the transition from healthy colonic epithelia through increasingly dysplastic adenoma to colorectal cancer.更多还原