Early Detection of Human Colorectal and Pancreatic Cancer

人类结直肠癌和胰腺癌的早期检测

• 批准号: 7246831
• 负责人: KENNETH W. KINZLER
• 金额: $ 27.24万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7246831
• 关键词: Biological Assay; Clinical; Colorectal; Colorectal Adenoma; Colorectal Cancer; Colorectal Neoplasms; DNA; Detection; Development; Diagnosis; Diagnostic Neoplasm Staging; Disease; Early Diagnosis; Feces; Future; Gastrointestinal Neoplasms; Genetic Predisposition to Disease; Genetic Research; Goals; Human; Individual; Lead; Malignant Neoplasms; Malignant neoplasm of gastrointestinal tract; Malignant neoplasm of pancreas; Molecular Genetics; Monitor; Morbidity - disease rate; Mutation; Mutation Detection; Neoplasms; Patient Care; Patients; Pattern; Plasma; Principal Investigator; Public Health; Registries; Residual Tumors; Sampling; Screening procedure; Somatic Mutation; Specificity; Staging; Technology; Testing; Translating; Tube; Validation; Work; adenoma; base; cancer therapy; clinically relevant; colorectal cancer screening; genetic analysis; improved; mortality; mutant; neoplastic cell; new technology; novel strategies; outcome forecast; pancreatic neoplasm; programs; prospective; size; tool; tumor

This project is a continuation of Project 1 A. Significant progress was made on each of the original aims of this project. Our goals related to improved presymptomatic diagnosis of individuals with inherited predispositions to cancer were essentially obtained and that aim has been retired. Our work related to early detection continued to show that somatic mutations can be sensitive and specific markers of neoplastic cells. Moreover, the development of a new technology called BEAMing, which allows hundred of thousands of individual PCRs to be performed in one tube, further improved our ability to detect somatic mutations. In total, our studies suggest that somatic mutations have the potential to significantly outperform conventional markers for early detection. Accordingly, our current proposal will focus on three aims related to the application of somatic mutations for the early detection of neoplasia. Aim #1 will focus on identification of somatic mutations in fecal DMAfor the early detection of colorectal cancers and adenomas. Specifically, we will develop and validate a Stool Mutation Test (SMT) capable of detecting clinically relevant adenomas and cancers with >70% and >90% sensitivity, respectively, and >99% specificity. Aim #2 will focus on identification of somatic mutations in plasma DMAfor the detection of colorectal cancers. The major goal of this aim is development and validation of a Plasma Mutation Test (PMT) capable of detecting early colorectal cancers (Dukes A and B) with >50% sensitivity and >99% specificity. Aim #3 will focus on identification of somatic mutations in plasma DMA for the early detection of pancreatic cancers. The goal of this aim is to develop and validate a PMT capable of detecting early pancreatic cancers (Stage I and II) with >50% sensitivity and >99% specificity. These studies will utilize samples from Cores 2 and 3 to translate discoveries made in former Projects 1A and 1B to patient care. We will provide tools for early screening of patients in Core 3 familial registries, help in the characterization of patients evaluated in Project 3A and aid development of new approaches by Projects 2B and 3B. The overall goal of the above studies is to provide clinically practical assays for early detection and management of colorectal and pancreatic cancers. From a public health prospective, such early detection strategies have the best chance of reducing the morbidity and mortality associated with colorectal and pancreatic cancers in the near term.

该项目是项目1的延续A.对每个原始目标取得了重大进展 这个项目。我们的目标与改善继承的人的预症状诊断有关 基本上获得了对癌症的易感性，该目标已退休。我们的工作与早期有关 检测继续表明，体细胞可能是肿瘤细胞的敏感和特定标记。 此外，开发了一种称为光束的新技术，该技术允许数十万 单个PCR将在一个管中进行，进一步提高了我们检测体突变的能力。在 总体而言，我们的研究表明，体细胞突变有可能明显胜过常规 早期检测的标记。因此，我们目前的提议将重点放在与 体细胞突变的应用用于肿瘤的早期检测。 AIM＃1将专注于识别 粪便中的体细胞突变，用于早期检测结直肠癌和腺瘤。具体来说，我们 将开发和验证能够检测临床相关腺瘤和的粪便突变测试（SMT） 具有> 70％和> 90％敏感性的癌症和> 99％的特异性。目标＃2将重点关注 血浆DMA中的体细胞突变的鉴定，用于检测结直肠癌。主要目标 这个目的是能够检测早期结直肠癌的血浆突变测试（PMT）的开发和验证 具有> 50％灵敏度和> 99％特异性的癌症（公爵A和B）。 AIM＃3将专注于识别 血浆DMA中的体细胞突变，用于早期检测胰腺癌。这个目标的目的是 开发和验证能够检测早期胰腺癌（I和II阶段）的PMT> 50％ 灵敏度和> 99％的特异性。这些研究将利用核2和3的样品翻译 以前项目1A和1B的发现进行了发现。我们将提供早期筛查的工具 核心3家族登记处的患者，有助于在项目3a中评估的患者的表征和辅助 通过项目2B和3B开发新方法。以上研究的总体目标是提供 临床上实用的测定法，用于早期检测和治疗结直肠癌和胰腺癌。来自 公共卫生的预期，这种早期检测策略有降低发病率和的最佳机会 在短期内与结直肠癌和胰腺癌相关的死亡率。