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结直肠腺瘤,单原发及多原发结直肠癌中P53及K-ras基因的突变分析

A Study on the Mutation of P53 and K-ras Gene in Colorectal Adenomas and Colorectal Carcinomas

  • 摘要: 【摘要】 目的 探讨结直肠腺瘤、单原发结直肠癌、多原发结直肠癌中P53及K-ras基因的突变。 方法 收集25例正常结直肠组织、38例结直肠腺瘤、78例单原发结直肠癌、19例(同时性多原发癌7例,异时性多原发癌12例)多原发结直肠癌组织标本及患者临床病理资料,提取标本组织中基因组DNA, 直接测序方法进行P53基因外显子5、6、7、8及K-ras基因密码子12、13序列分析,并对结直肠腺瘤及单原发结直肠癌的临床资料与其P53及K-ras基因突变进行多因素相关性分析。 结果 正常结直肠组织、结直肠腺瘤、单原发结直肠癌、多原发结直肠癌中P53基因的突变概率分别是0%(0/25)、44.8%(17/38)、43.6%(34/78)、42.1%(8/19),K-ras基因的突变概率分别为0%(0/25)、18.4%(7/38)、39.7%(31/78)、47.4%(9/19),正常结直肠组织中P53和K-ras基因突变概率与结直肠腺瘤、单原发结直肠癌、多原发结直肠癌中突变概率相比,差异均有统计学意义(P<0.05),结直肠腺瘤中K-ras基因突变概率与单原发结直肠癌、多原发结直肠癌中突变概率相比,差异均有统计学意义(P<0.05),结直肠腺瘤中P53基因突变概率高于K-ras基因(P<0.05)。P53及K-ras基因在单原发结直肠癌的Ⅰ、Ⅱ期及高分化类型中的突变概率与其在Ⅲ、Ⅳ期及中低分化类型中差异无统计学意义。患者的年龄、性别、家族史、肿瘤位置与结直肠腺瘤及单原发结直肠癌中P53及K-ras基因突变无相关性,肿瘤分期及肿瘤的分化程度亦不是单原发结直肠癌中P53及K-ras基因发生突变的危险因素。 结论 本研究再次证实在结直肠肿瘤的发生和发展过程中,P53及K-ras基因的突变起着重要的作用,并且在结直肠的肿瘤发生发展过程中P53基因的突变可能早于K-ras基因。

     

    Abstract: 【Abstract】 Objective To investigate the incidence of P53 and K-ras gene mutation in colorectal adenomas and primary colorectal carcinomas. Methods There were 25 normal samples, 38 samples of colorectal adenoma, 78 samples of single primary colorectal cancer and 19 samples of multiple primary colorectal carcinomas (7 synchronous colorectal carcinomas and 12 metachronous colorectal carcinomas) collected in this study. With the analysis of clinico-pathologic features for each patient, exon 5-8 of P53 gene and codon 12-13 of K-ras gene of each sample were extended by real-time PCR. Multi-factor correlation analysis was carried out between the clinicopathologic features and the mutation of P53 and K-ras gene in colorectal adenoma and primary colorectal cancer. Results The P53 gene mutation is 0% (0/25),44.8%(17/38),43.6%(34/78)and 42.1%(8/19)respectively in normal mucosa tissue, colorectal adenomas, single lesion and multiple lesion of primary colorectal carcinomas, while the proportion of K-ras gene mutation was 0%(0/25),18.4%(7/38),39.7%(31/78),47.4%(9/19)respectively. In our investigation there were obvious statistical differences as to the proportion of mutation of the P53 and K-ras gene between normal mucosa tissue and other three groups respectively (P<0.05), while statistical differences as to the proportion of mutation of K-ras gene were found between colorectal adenomas group and single or multiple colorectal carcinoma group (P<0.05). There was significant statistical difference between P53 and K-ras gene mutation in colorectal adenomas (P<0.05). In addition, there were no statistical differences as to the proportion of mutation of the P53 and K-ras gene between the stageⅠ,Ⅱand well-differentiated ones of primary colorectal cancers and the stageⅢ Ⅳ and poorly-differentiated ones. There was no relationship between the age, gender, family history and tumor locations of the patients and the mutation of the P53 and K-ras gene. The stage and grade of differentiation of cancer was not the risky factor of the mutation of the P53 and K-ras gene in primary colorectal cancers. Conclusion The cancers. Conclusion results of this study not only suggest that mutation of P53 suppressor gene and K ras play a significant role in the procedure of colorectal tumorigenesis, but also indicate that the mutati on of P53 gene occurs earlier than K-ras mutation does during tumorigenesis.

     

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