Early Detection of Human Colorectal and Pancreatic Cancer

该项目是项目1A的延续。在每一个最初的目标上都取得了重大进展， 这个项目我们的目标是改善遗传性乳腺癌患者的症状前诊断。 基本上获得了癌症的易感性，并且该目标已经退休。我们的工作与早期 检测继续显示体细胞突变可以是肿瘤细胞的敏感和特异性标志物。 此外，一种名为BEAMing的新技术的发展， 在一个试管中进行单独的PCR，进一步提高了我们检测体细胞突变的能力。在 总的来说，我们的研究表明，体细胞突变有可能显着优于传统的 早期检测的标记。因此，我们目前的建议将侧重于与以下方面有关的三个目标： 体细胞突变在肿瘤早期检测中的应用。目标1将侧重于识别 粪便DMA中的体细胞突变用于结直肠癌和腺瘤的早期检测。我们特别 将开发和验证能够检测临床相关腺瘤的粪便突变试验（SMT）， 敏感性分别>70%和>90%，特异性>99%。目标#2将重点放在 鉴定血浆DMA中的体细胞突变以检测结直肠癌。的主要目标 目的是开发和验证能够检测早期结直肠癌的血浆突变试验（PMT）， 癌症（Dukes A和B），灵敏度>50%，特异性>99%。目标3将侧重于识别 血浆DMA中的体细胞突变用于胰腺癌的早期检测。这一目标的目的是 开发并验证能够检测早期胰腺癌（I期和II期）的PMT， 灵敏度和>99%特异性。这些研究将利用核心2和3的样本进行翻译 在以前的项目1A和1B中发现了病人护理。我们将提供工具， 核心3家族登记研究中的患者，有助于描述项目3A中评价的患者的特征， 项目2B和3B开发新方法。上述研究的总体目标是提供 用于结肠直肠癌和胰腺癌的早期检测和管理的临床实用测定。从 从公共卫生的角度来看，这种早期发现策略最有可能降低发病率， 与结直肠癌和胰腺癌相关的近期死亡率。

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.