SCREENING PRETEST FOR HEREDITARY COLON CANCER (HNPCC)

我们的目标是开发一种诊断分析方法来识别携带者

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.