RAPID CANCER PREDISPOSITION SCREEN FOR GENE MUTATIONS

TreviMed has developed a novel patent pending technology, Oscillating Cleavage Amplification Reaction (OsCAR), for the detection of point mutations in clinical samples. The entire assay will take about one hour from preparation of the DNA sample and will utilize capillary electrophoretic separation, which presently takes about two minutes. Presently, the assay detects attomole levels of target using its inherent signal amplification technology. The technology is extremely cost effective and automatable, making it attractive for large scale screening. OsCAR does not require PCR, which has been shown to be problematic for mismatch detection due to the generation of point mutations by the synthetic amplification step. In this proposal, we plan to apply Oscar to the detection of human mismatch repair enzymes implicated in hereditary nonpolyposis colon cancer (HNPCC), which is inherited in an autosomal dominant fashion resulting in colorectal cancer, and less frequently in ovary and endometrial tumors. The large gene size (73 kbp) and organization (16 exons) makes DNA sequencing and other approaches challenging, making OsCAR detection of specific high frequency mutations more practical.