SCREENING PRETEST FOR HEREDITARY COLON CANCER (HNPCC)

描述：我们的目标是开发一种诊断方法，以确定载体的 遗传性结肠癌（HNPCC）性状使用血液样本作为输入， 试样在第1阶段，我们将证明该检测方法的可行性，显示：1） 必要的预测值，2）实用性（容易，快速，便宜），和3） 适应自动化技术。我们的检测应该能检测出 DNA错配修复（MMR）基因（MLH 1和MSH 2）的变化， HNPCC个体由于MLH 1或MSH 2两个等位基因之一突变 基因我们已经初步证明了这种策略的可行性。 模型，其中测定结果与野生型基因状态相关。我们 目的是：1）开发一种MMR突变的预测测定法， 准确地证明测定结果与基因型相关; 1b） 区分野生型纯合细胞和杂合细胞 等位基因和具有和不具有HNPCC性状的个体之间; 2）适应 我们的分析与自动化系统一起工作。这将导致我们的第二阶段 目的：将我们的分析整合到定量，商业，自动化 系统. 拟定商业应用： 我们的检测方法的商业应用包括遗传性非息肉病的实际检测 结肠癌（HNPCC）在西方世界影响超过500万人。 检测 HNPCC在癌症发展之前提供了临床益处，因为癌症预防策略 降低他们的死亡率。 如果技术上可行（第1阶段），我们的检测方法成为 商业化（第2阶段）是由于该项目的强有力的承诺， 拜耳诊断公司，该公司在全国范围内销售自动诊断系统。

DESCRIPTION: Our goal is to develop a diagnostic assay to identify carriers of the hereditary colon cancer (HNPCC) trait using blood samples as the input specimen. In Phase 1 we will demonstrate the assay's feasibility, showing: 1) requisite predictive value, 2) practicality (easy, rapid, inexpensive), and 3) adaptability to automated technologies. Our assay should detect cellular changes in DNA mismatch repair (MMR) genes (MLH1 & MSH2), changes that occur in HNPCC individuals due to mutation of one of the two alleles of the MLH1 or MSH2 gene. We already demonstrated plausibility for this strategy in preliminary models in which the assay outcome correlated with wild-type gene status. Our AIMS are: 1) to develop a predictive assay for MMR mutations that 1a) accurately demonstrates that the assay outcome correlates with genotype; 1b) distinguishes between cells homozygous and those heterozygous for the wild-type allele and between individuals with and without the HNPCC trait; 2) to adapt our assay to work with automated systems. This will lead to our Phase 2 objective: to integrate our assay into quantitative, commercial, automated systems. PROPOSED COMMERCIAL APPLICATION: The commercial application of our assay involves a practical test for hereditary nonpolyposis colon cancer (HNPCC) affecting over 5 million people in the western world. Detecting HNPCC before cancer develops offers a clinical benefit since cancer prevention strategies reduce their mortality. If technically feasible (Phase 1), the likelihood of our assay becoming commercialized (Phase 2) is outsanding because of the strong commitment of this project by Bayer Diagnostics, which nationally distributes automated diagnostic systems.