A new molecular diagnosis of stomach cancer determined by CGH and quantitative real time microsatellite analysis

通过 CGH 和定量实时微卫星分析确定胃癌的新分子诊断

• 批准号: 13671351
• 负责人: SUZUKI Seiji
• 金额: $ 2.24万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671351/
• 关键词: CGH; Quantitative real time microsatellite analysis; Microsatellite marker; Stomach cancer; ZNF217; D8S1801; D16S3026; DNA copy number aberration; genetic instability; 定量的real timeマイクロサテライト分析法; Chromosomal instability; DOP-PCR

We detected the relative DNA copy numbers (RCNs) at the target loci in thirty patients with stomach cancer, with quantitative microsatellite analysis (QuMA), Seven microsatellite loci in chromosome 8q (D8S530,D851724,D851801) 16q (D1653140,D1653026) and 20q (D205911,D205185) and one gene specific locus (ZNF217) were selected as the target loci. The RCN was obtained relatively to a pooled reference cocsisting of six microsatellite promer sets selected from the regions where few aberrations have been observed in comparative genomic hybridization (CGH) analysis. Based on the TaqMan PCR system, internal probes used were carring donor (FAM) and acceptor (TAMRA) fluorescent molecules complementary to CA repeat in the microsatellite markers and to one gene specific oligomer in the gene specific marker. Chromosome 8q gain, 20q gain and 16q loss were detected in 18 (60%), 8 (26.7%) and 13 cases (43,3%), respectively. Gains in the RCNs of D8S1801 and D8S1724 were most frequently found (36.7%). There was a significant correlation between the loss of D16S3026 and reduced survival duration (P0.0158), and the simultaneous aberrations of D8S1801 gain and D16S3026 loss (Double marker positive) was significantly associated with reduced survival duration (P=0.0008). According to Cox proportional hazard model, the double marker posive was a significant and independent factor indicationg an unfavorable prognostic factor (RR:17.176,95% Cl:2.782-106.026, P=0.0022). RCN aberrations in tumor tissues determined by QuMA enable to identify the prognostic factors that correlate with clinical outcome of the patients with stomach cancer.

应用微卫星定量分析技术（QuMA）检测了30例胃癌患者靶位点的相对DNA拷贝数（RCNs）。选择D8 S530、D851724、D851801、16 q（D1653140、D1653026）、20 q（D205911、D205185）和1个基因特异位点（ZNF 217）作为靶位点。RCN是相对于从比较基因组杂交（CGH）分析中观察到很少畸变的区域中选择的6个微卫星引物集的合并参考而获得的。在TaqMan PCR系统的基础上，使用的内部探针携带与微卫星标记中的CA重复序列互补的供体（FAM）和受体（塔姆拉）荧光分子，以及与基因特异性标记中的一个基因特异性寡聚体互补的受体荧光分子。染色体8 q增加18例（60%），20 q增加8例（26.7%），16 q丢失13例（43.3%）。D8 S1801和D8 S1724的RCN增加最常见（36.7%）。D16 S3026缺失与生存期缩短显著相关（P0.0158），D8 S1801获得和D16 S3026缺失（双标记阳性）同时畸变与生存期缩短显著相关（P=0.0008）。根据考克斯比例风险模型，双标记物阳性是预后不良的独立危险因素（RR：17.176，95% CI：2.782-106.026，P=0.0022）。通过QuMA确定的肿瘤组织中的RCN畸变能够识别与胃癌患者临床结局相关的预后因素。

项目成果

Seiji Suzuki, Kaku Egami et al.: "Comparative study between DNA copy number aberrations determined by quantitative microsatellite analysis and clinical outcome in patients with stomach cancer"Clinical Cancer Research. (In press). (2004)

Seiji Suzuki、Kaku Egami 等人：“通过定量微卫星分析确定的 DNA 拷贝数畸变与胃癌患者临床结果之间的比较研究”临床癌症研究。

Seiji Suzuki, Kaku Egami et al.: "Comparative study between DNA copy number aberrations determine by quantitative real time microsatellite analysis and clinical outcome in patients with stomach cancer"Clinical Cancer Research. (In press). (2004)

Seiji Suzuki、Kaku Egami 等人：“通过定量实时微卫星分析确定的 DNA 拷贝数畸变与胃癌患者临床结果之间的比较研究”临床癌症研究。

Seiji Suzuki, Kaku Egami et al.: "Comparative study between DNA copy number aberrations determined by quantitative real time microsatellite analysisi and clinical outcome in patients with stomach cancer"Clinical Cancer Research. in press. (2004)

Seiji Suzuki、Kaku Egami 等人：“通过定量实时微卫星分析确定的 DNA 拷贝数畸变与胃癌患者临床结果之间的比较研究”临床癌症研究。