LASER-CAPTURE MICRODISSECTION - OPENING THE MICROSCOPIC FRONTIER TO MOLECULAR ANALYSIS

As the list of expressed human genes expands, a major scientific chall enge is to understand tbe molecular events that drive normal tissue mo rphogenesis and the evolution of pathological lesions in actual tissue . Laser capture microdissection (LCM) has been developed ro provide a reliable method to procure pure populations of cells from specific mic roscopic regions of tissue sections, in one step tenner direct visuali zation. The cells of interest are transferred to a polymer film that i s activated by laser pulses. The exact morphology of the procured cell s (with intact DNA, RNA and proteins) is retained and held on the tran sfer film. With the advent of LCM, cDNA libraries can be developed fro m pure cells obtained directly from stained tissue, and microhybridiza tion arrays of thousands of genes can now be used to examine gene expr ession in microdissected human tissue biopsies. The fluctuation of exp ressed genes or alterations in the cellular DNA that correlate with a particular disease stage can ultimately be compared within or between individual patients. Such a fingerprint of gene-expression patterns ca ll provide crucial clues for etiology and might, ultimately, contribut e to diagnostic decisions and therapies tailored to the individual pat ient. Molecules found to be associated with a defined pathological les ion might serve as imaging or therapeutic targets.