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Clonality analysis of neuroendocrine cells in gastric adenocarcinoma

机译:胃腺癌神经内分泌细胞的克隆性分析

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AIM: To achieve a better understanding of the origination of neuroendocrine (NE) cells in gastric adenocarcinoma. METHODS: In this study, 120 cases of gastric adenocarcinoma were obtained. First, frozen section-immunohistochemistrical samples were selected from a large quantity of neuroendocrine cells. Second, laser capture microdissection was used to get target cells from gastric adenocarcinoma and whole genome amplification was applied to get a large quantity of DNA for further study. Third, genome-wide microsatellite abnormalities [microsatellite instability (MSI), loss of heterozygosity (LOH)] and p53 mutation were detected by polymerase chain reaction (PCR)-single-strand conformation polymer- phism-silver staining and PCR-sequencing in order to identify the clonality of NE cells. RESULTS: The total incidence rate of MSI was 27.4%, while LOH was 17.9%. Ten cases had a highest concordance for the two types of cells. The other samples had similar microsatellite changes, except for cases 7 and 10. Concordant p53 mutations exhibited in sample 4, 14, 21 and 27, and there were different mutations between two kinds of cells in case 7. In case 17, mutation took place only in adenocarcinoma cells. p53 mutation was closely related with degree of differentiation, tumor-node-metastasis stage, vessel invasion and lymph node metastasis. In brief, NE and adenocarcinoma cells showed the same MSI, LOH or p53 mutation in most cases (27/30). In the other three cases, different MSI, LOH or p53 mutation occurred. CONCLUSION: NE and the gastric adenocarcinoma cells may mainly derive from the same stem cells, but the remaining cases showing different origin needs further investigation.
机译:目的:为了更好地了解胃腺癌中神经内分泌(NE)细胞的起源。方法:本研究共获得120例胃腺癌。首先,从大量神经内分泌细胞中选择冷冻切片-免疫组织化学样品。其次,使用激光捕获显微切割技术从胃腺癌中获取靶细胞,并通过全基因组扩增获得大量DNA,以供进一步研究。第三,通过聚合酶链反应(PCR)-单链构象-多态性-银染和PCR-测序依次检测全基因组微卫星异常[微卫星不稳定性(MSI),杂合性缺失(LOH)]和p53突变。识别NE细胞的克隆性。结果:MSI总发生率为27.4%,LOH为17.9%。十个案例对两种类型的单元格的一致性最高。除情况7和10外,其他样品的微卫星变化相似。在样品4、14、21和27中出现了一致的p53突变,在情况7中两种细胞之间存在不同的突变。在情况17中,发生了突变仅在腺癌细胞中。 p53突变与分化程度,肿瘤淋巴结转移阶段,血管浸润和淋巴结转移密切相关。简而言之,在大多数情况下,NE和腺癌细胞显示出相同的MSI,LOH或p53突变(27/30)。在其他三种情况下,发生了不同的MSI,LOH或p53突变。结论:NE和胃腺癌细胞可能主要来源于相同的干细胞,但其余病例显示出不同的来源需要进一步研究。

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