Comparative genome hybridization.

This technique reveals the loss or gain of chromosomal regions in test samples (for example, derived from a tumour) relative to normal controls. DNA in the test and reference samples is labelled with green and red fluorochromes, respectively, and allowed to compete for hybridization sites on either metaphase chromosomes (left) or an array of BAC (bacterial artificial chromosome) clones that represent thousands of small DNA segments distributed across the genome (right). Areas on the chromosome, or spots on the array, that are more green than average are present in extra copies in the test sample; those that are more red than average are deleted in the test sample. The bottom left panel shows the outcome of conventional comparative genome hybridization using the prostate-cancer cell line PC-3 as a test sample; the loss and gain of several chromosomal regions are evident as red and green areas, respectively. Inset: the profile of the average green:red ratio of ten chromosomes shows 8p loss and 8q gain in these cells. The bottom right panel shows copy-number losses of 1p, 6q, 11q and 20p, and gains of 12, 13 and 20q in the ML-2 cancer cell line. Bottom left panel provided by Ilona Holcomb, Fred Hutchinson Cancer Research Center; bottom right panel reproduced with permission from BAC Resource Consortium. Integration of cytogenetic landmarks into the draft sequence of the human genome. Nature 409, 953–958 (2001). © (2001) Macmillan Magazines Ltd.