散发性结直肠癌D10S1265位点的杂合缺失分析

The Study of Loss of Heterozygosity on D10S1265 Locus in 83 Sporadic Colorectal Carcinomas

目的:染色体上某特定位点遗传物质的丢失是肿瘤发生中的常见现象,抑癌基因的杂合缺失是结直肠癌形成中的关键步骤之一。本实验通过对83例散发性结直肠癌中D10S1265位点杂合缺失的研究,探讨其在结直肠癌演变中的作用。方法:荧光标记的多态性微卫星引物D10S1265与83例结直肠癌的肿瘤和正常组织进行PCR反应。PCR产物在ABIPrism377自动荧光测序仪电泳3h,以GeneScan3.1和Genotyper2.1软件进行扫描以及杂合缺失分析。其结果与临床病理因素进行卡方检验。结果:D10S1265位点(10q24.3)的杂合缺失率是50.0%,肝转移的7例未发现LOH,无肝转移病例达58.97%(23/39,P=0.014),但与淋巴结转移无关。另外,此位点的杂合缺失与Dukes'分期显著相关(P=0.013),与其他临床病理因素无关。结论:D10S1265位点附近可能存在与散发性结直肠癌有关的抑癌基因,此基因与结直肠癌的进展和肝转移相关。

Objective: The loss of genetic material from specific chromosome loci is a common feature in the tumorigenesis and is often indicative of the presence of important tumor suppressor genes(TSG) at these loci. Loss of heterozygosity(LOH) is one of the important procedure to detect TSG. The aim of this study is to identify additional loci involved in sporadic colorectal carcinoma(CRC). Methods: D10S1265, a fluorescent labeled polymorphic microsatellite marker, was analyzed in 83 cases of sporadic CRC and normal tissue DNA by PCR. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.1 and Genotype 2.1 software were used for LOH scanning and analysis. Comparison between LOH frequency and clinicopathological factors were performed by χ2 test. Results: The LOH frequency of D10S1265 locus (10q24.3) was 50.0%. On this locus, there was no LOH accompanied within liver metastasis patients(0/7), while 58.97%(23/39) without liver metastasis (P=0.014). Additional significant correlation was detected between LOH frequency and Dukes stages (P=0.013). Conclusion: This study seems to show the evidence of the TSG on 10q24.3 related to the sporadic CRC, which may be involved in the progression and metastasis.