胃癌微卫星不稳定性和抑癌基因杂合缺失

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目的研究微卫星不稳和抑癌基因缺失在胃癌发生中的作用.方法采用PCR为基础的方法,检测了53例胃癌中6个微卫星标记突变及APC/MCC和DCC基因杂合缺失(LOH).结果胃癌微卫星不稳的检出率为321%(17/53).7例(132%)为微卫星高频率不稳(3个以上微卫星标志),10例(189%)为微卫星低频率不稳(1或2个微卫星标记).肠型胃癌微卫星高频率不稳的发生率(250%)显著高于弥漫型胃癌(34%)(P<005).高频率不稳组未发现有APC,MCC和DCC基因LOH,微卫星高频率不稳与APC/MCC和DCC基因LOH呈负相关.结论微卫星不稳在部分胃癌,特别是肠型胃癌早期发生中起重要作用,高频率不稳胃癌与遗传性非息肉大肠癌有共同的特点.与此相反,低频率不稳和无不稳胃癌可能通过LOH病理途径发生 4. Objective To study the role of microsatellite instability and tumor suppressor gene deletion in gastric carcinogenesis. Methods PCR-based methods were used to detect six microsatellite marker mutations and loss of heterozygosity (LOH) in APC/MCC and DCC genes in 53 cases of gastric cancer. Results The detection rate of gastric cancer microsatellite instability was 32.1% (17/53). Seven cases (132%) were microsatellite high frequency instability (more than 3 microsatellite markers), and 10 cases (189%) were microsatellite low frequency instability (1 or 2 microsatellite markers). The incidence of microsatellite high frequency instability (25.0%) in intestinal type gastric cancer was significantly higher than that in diffuse type gastric cancer (3.4%) (P < 0.05). In the high-frequency unstable group, there was no LOH of APC, MCC and DCC genes. A high frequency of microsatellite instability was negatively correlated with APC/MCC and LOH gene LOH. Conclusion Microsatellite instability plays an important role in the early development of gastric cancer, especially in intestinal type gastric cancer. High-frequency unstable gastric cancer has common features with hereditary non-polypoid colorectal cancer. In contrast, low frequency instability and instability of gastric cancer may occur through the pathological pathway of LOH.
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