Genetic diagnosis of gastrointestinal cancer using peripheral blood DNA or ascitis DNA

利用外周血DNA或腹水DNA进行胃肠道癌症的基因诊断

• 批准号: 11671240
• 负责人: ISOZAKI Hiroshi
• 金额: $ 2.37万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671240/
• 关键词: pancreatic cancer; serum DNA; LOII; microsatellite inslability; genetic instability; 膵癌; 血漿; DNA; 末梢血; plasma; peripheral blood

Evidences of circulating soluble DNA in bloodstream of cancer patients has emerged. Because the plasma DNA is largely derived from cancer cells, genetic analysis of plasma DNA is important to understand the molecular events occurred in cancer patient. Seven microsatellite markers in the soluble plasma DNA from patients with pancreatic adenocarcinoma and other paucreato-biliary malignant tumors were examined for microsatellite instability (MSI) and allelic imbalance (AI). As the result, a variety of genetic alterations including MSI and AI were detected in the plasma DNA. Some alterations were detected before recurrence of the tumor was verified. Analysis of five primary pancreatic adenocarcinomas by microdissection revealed that the heterogenous nature of pancreatic tumors is associated with both MSI and AI in the same tumor. The presence of altered plasma DNA including MSI and/or AI from the same pancreatic cancer patient may be important evidence for the presence of theses alterations in heterogenous primary tumor. Analysis of plasma DNA could hopefully become one of the diagnostic or therapeutic measure for this formidable pancreatic adenocarcinoma.

癌症患者血液中循环可溶性DNA的证据已经出现。由于血浆DNA主要来源于癌细胞，因此血浆DNA的遗传分析对于了解癌症患者中发生的分子事件是重要的。对胰腺癌和其他少血胆系恶性肿瘤患者血浆可溶性DNA中的7个微卫星标记进行了微卫星不稳定性（MSI）和等位基因失衡（AI）检测。结果，在血浆DNA中检测到包括MSI和AI在内的多种遗传改变。在确认肿瘤复发之前检测到一些改变。通过显微解剖分析5例原发性胰腺癌，发现胰腺肿瘤的异质性与同一肿瘤的MSI和AI相关。来自同一胰腺癌患者的改变的血浆DNA（包括MSI和/或AI）的存在可能是异质性原发肿瘤中存在这些改变的重要证据。血浆DNA分析有望成为胰腺癌的诊断或治疗手段之一。

项目成果

Matsubara N, et al.: "Role of E2F-4 mutations in chemosensitivy"Proc. Annu. Meet. Am. Assoc. Cancer Res.. 40. A2822 (1999)

Matsubara N 等：“E2F-4 突变在化学敏感性中的作用”Proc。

Matsubara N, et al.: "Multiple tumors and a novel E2F-4 mutation"Digestion. 62. 213-216 (2000)

Matsubara N 等人：“多种肿瘤和新型 E2F-4 突变”消化。

馬場正三他: "21世紀の大腸癌診断治療戦略のために HNPCC in the year2000"株式会社マイライフ社. 71 (2000)

Shozo Baba等：“2000年21世纪HNPCC的结直肠癌诊断和治疗策略” My Life Co., Ltd. 71 (2000)

Matsubara N, et al: "The farthest 3' distal end APC mutation identified in attenuated adenomatous polyposis coli with extracolonic manifestations."Dis.Colon Rectum. 43・5. 720-721 (2000)

Matsubara N 等人：“在具有结肠外表现的减毒腺瘤性息肉病中鉴定出最远的 3 远端 APC 突变。”Dis.Colon Rectum。 720-721 (2000)。

松原長秀 他: "大腸癌の遺伝子変異と臨床応用の可能性."日本外科学会雑誌. 101・6. 468-475 (2000)

Nagahide Matsubara 等：“结直肠癌的基因突变及其临床应用的可能性。”日本外科学会杂志 101・6（2000 年）。