SCREENING PRETEST FOR HEREDITARY COLON CANCER (HNPCC)

描述：我们的目标是开发一种诊断分析方法来识别携带者 以血液样本为输入的遗传性结肠癌(HNPCC)特征 样本。在第一阶段，我们将论证该分析的可行性，显示：1) 必备的预测值；2)实用性(简单、快速、廉价)；3) 对自动化技术的适应性。我们的化验应该能检测到细胞 DNA错配修复(MMR)基因(MLH1和MSH2)的变化，发生在 MLH1或MSH2两个等位基因中的一个突变导致的HNPCC个体 吉恩。我们已经初步证明了这一策略的可行性。 检测结果与野生型基因状态相关的模型。我们的 目标是：1)开发一种预测MMR突变的方法 准确地证明检测结果与基因相关；1b) 区分野生型纯合子细胞和杂合子细胞 具有和不具有HNPCC特征的个体之间的等位基因；2)适应 我们的化验工作与自动化系统。这将导致我们的第二阶段 目的：将我们的检测方法集成到定量、商业化、自动化 系统。 建议的商业应用： 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)在西方世界影响着500多万人。检测 癌症发生前的HNPCC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(第一阶段)，我们的化验结果成为 商业化(第二阶段)由于该项目的坚定承诺而告终 拜耳诊断公司是一家在全国范围内分销自动诊断系统的公司。

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.