which application of these tests now appears most informative, and finally contains several recommendations concerning the ways in which the medical community should prepare itself for the widespread implementation of these tests in clinical practice. (Table 2-1 provides an overview of the status of genetic testing for cancer.)
Many of the methods now used to detect tumor markers identify changes in DNA structure or sequence directly. However, because genetic information encoded in DNA is transcribed into RNA and finally translated into protein, tests that assess RNA sequence or quantity, or protein structure, function, or quantity, are also informative in various situations. The molecular lesions associated with different kinds of tumors are diverse, necessitating a pragmatic approach suited to the individual type of tumor in question.
Until recently, detection of chromosomal rearrangements has been dependent on cytogenetic analysis. Briefly, fresh tumor cells are disaggregated and grown for short periods of time in cell culture. Growing cells are then poisoned with a chemical that arrests the cells in metaphase, a stage in cell division (mitosis) during which DNA is condensed into readily recognizable chromosomes. The cells are then swollen in a hypotonic solution, fixed, and dropped onto glass slides. The slides are pretreated to induce banding and are stained with a dye that binds to the chromosomes. The chromosomes are analyzed under the microscope. Sets of chromosomes dispersed from single cells are then photographed, and each chromosome is cut from the photograph and assembled in an orderly portrait, or karyotype, showing the total chromosomal content of an individual cell.
To interpret cytogenetic data, a working understanding of the structural components of chromosomes and the nomenclature used to describe them is required. The normal diploid human cell contains 46 chromosomes, composed of 22 pairs of autosomes (numbered 1–22) and 2 sex chromosomes (two X chromosomes in the female, one X and one Y chromosome in the male). Each chromosome has a constriction called a centromere that divides the chromosome into two arms; the long arm is designated ''q'' and the short arm "p." The arms of each chromosome contain a characteristic pattern of light and dark bands revealed by staining the chromosomes with a variety of dyes, and each band is identified by a number.
The karyotype of an individual cell is reported as a list describing the number of chromosomes, the sex chromosomes present, and any observed abnormalities. For example, a normal karyotype for a female is 46,XX; for a male 46,XY. Abnormalities of chromosome number are referred to as aneuploidy and most commonly include the presence of an additional copy