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In 1969 visualization of nucleic acid sequences in situ was first described using isotopically labeled rRNA (Gall and Pardue 1969). Since then, in situ hybridization employing radioactively labeled probes has been widely used. With the advent of nonisotopic procedures for labelling nucleic acids in the early 1980s, fluorescence in situ hybridization (FISH) was developed and has become increasingly popular. Compared with radioactive in situ hybridization, FISH has a number of specific advantages including increases in speed, sensitivity and resolution (for review see Raap et al. 1990; Lichter and Ward 1990; Trask 1991).

Analysis of chromosomal DNA by fluorescence in situ hybridization (FISH) is used in many areas of biological research as well as in clinical cytogenetics. A major advantage of this method for the clinical applications is that chromosomal changes can be diagnosed not only on metaphase chromosomes but also in interphase nuclei (see Figure 1 and Chap. 12). Thus, the analysis is not dependent on the preparation of metaphase chromosomes, which are often difficult or impossible to obtain. Furthermore, preparation of metaphase chromosomes often requires stimulation of cells by mitogens. Such mitogenic stimulation frequently results in selective growth of a subset of cells in the sample. This may lead to the diagnosis of chromosomal aberrations that do not reflect the composition of the tumor in vivo.

During the last decade strong evidence has been accumulated for a causal relationship between specific genetic alterations and the abnormal differentiation state and growth behaviour of malignant cells. Such alterations can be observed at different levels ranging from chromosome mutations to point mutations of certain genes and may arise in a given cell either spontaneously or due to the effect of mutagenic environmental factors.