Development of Serum Based Biomarker for the Detection of Cancer

"We propose an innovative technique for ultra rapid, sensitive detection ofcancer specific chromosome rearrangements in solution to facilitate bulkquantification of aberrant chromosomes for early detection of metastatictumor cells. (I) We will apply DNA hybridization in suspension to humanbreast cancer cell lines by combining two separate, novel techniques 1)hybridizing chromosomes in suspension; 2) using repeat sequence deplete DNAprobes in combination with a flow cytometric method of analysis and magneticsorting, in order to sensitively, precisely and rapidly quantifycancer-related chromosome translocations and rearrangements. Chromosomeaberrations will be detected using reversible DNA-hybridization probes thatuniquely bind to DNA normally present in a specific subset of the genome. Asecond set of reversible DNA hybridization probes will be used to uniquelyhybridize with a corresponding second subset of the genome. Any (aberrant)chromosomes containing both subsets will be rapidly and efficiently isolatedand quantified. (II) We will determine the translocation detectionsensitivity (has a potential sensitivity of 1x1,000,000) using serialdilutions of a human breast cancer cell line with known translocation withthe lymphoblast cell line AG122. We expect our technique will havesensitivity similar to PCR and far higher than FISH, with specificity betterthan PCR."