The role of fluorescence in situ hybridization technologies in molecular diagnostics and disease management

Large genomic changes, such as aneuploidy, deletions, and other chromosomal rearrangements, have long been associated with pregnancy loss, congenital abnormalities, and malignancy. These genomic changes are quantitative, unam biguous, and fundamental in the transition of normal cells to abnormal ones . Detection of these large genetic changes has an increasingly important ro le in determining patient diagnosis and care, including therapeutic selecti on. We have developed two major product platforms that assess genomic chang es at various levels of resolution. Fluorescence in situ hybridization (FIS H) techniques and the related technology of array-based comparative genomic hybridization (CGH) allow detection of gene-sized or larger alterations in the genome. FISH is a robust DNA probe technology that can measure both ba lanced and unbalanced genomic changes on a cell-by-cell basis. In most inst ances, it is not dependent on metaphase chromosomes, and it is widely used in clinical diagnostics. Array-based CGH has much greater multiplexing capa bilities than FISH. This technology has the potential to examine many regio ns of the genome simultaneously for changes in DNA copy number and identify complex patterns of gains and losses within the genome. In this article, w e review several of the current medical applications of FISH and discuss su ch advanced techniques as CGH and array-based CGH.