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目的 许多研究表明在伴有微卫星不稳定性(MicroSatellite Instability,MSI)的遗传性结直肠癌中,β-转化生长因子Ⅱ型受体(Transfonning Growth Factor-βTypeⅡReceptor,TGF-βRⅡ)基因突变频繁,极可能是其发生的重要机制;并且TGF-RⅡ基因的(A)_(10)重复序列是MSI的靶点。但在散发性结直肠癌中报道较少,本研究通过对散发性结直肠癌的MSI及TGF-RⅡ基因突变的枪测,以期了解它们在散发性结直肠癌发生中的作用 方法 选取单态性很强的BAT-26微卫星位点,应用PCR等分子生物学手段检测MSI;应用PCR-SSCP-银染法-测序检测RⅡ基因突变 结果 有13例(26％)为MSI,近端(42.11％)明显高于远端者(16.13％)(P<0.05),RⅡ基因的突变率为10％(5/50),表现为RⅡ基因的(A)_(10)重复序列出现一个A的缺失导致框架移位突变(Frame Shift Mutation),伴有MSI的肿瘤中RⅡ突变率为38.46％,所有RⅡ突变者均伴有MSI,而无MSI的肿瘤中均无RⅡ突变(P<0.01) 结论 不仅在HNPCC中,而且在散发性结直肠癌中,TGF-RⅡ基因的(A)_(10)重复序列是MSI的靶点。
OBJECTIVES: Many studies have shown that mutations in the transforming growth factor-β receptor (TGF-βRII) are frequent in inherited colorectal cancers with microsatellite instability (MSI). It is highly likely to be an important mechanism for its occurrence; and the (A)_(10) repeat of the TGF-RII gene is the target of MSI. However, there are few reports in sporadic colorectal cancer. In this study, the MSI and TGF-RII gene mutations in sporadic colorectal cancer were measured by guns in order to understand their role in sporadic colorectal cancer. The BAT-26 microsatellite locus was very strong, and MSI was detected by molecular biology methods such as PCR; and 13 cases (26%) of MSI were detected by PCR-SSCP-silver staining-sequencing. 42.11%) was significantly higher (16.13%) than distal (16.13%) (P<0.05). The mutation rate of RII gene was 10% (5/50). The appearance of (A)_(10) repeat sequence of RII gene was an A. The deletion resulted in a frame shift mutation, and the RII mutation rate in MSI-associated tumors was 38.46%. All RII mutations were accompanied by MSI, while none of the MSI-negative tumors had RII mutations (P<0.01). Conclusions The (A)_(10) repeats of TGF-RII gene are targets of MSI not only in HNPCC but also in sporadic colorectal cancer.