Genomic Gains and Losses

DNA repair genes are thought to be the body's frontline defense against mutations and, as such, play a major role in cancer. Mutations within these genes often manifest themselves as lost or broken chromosomes. It has been hypothesized that certain chromosomal gains and losses are related to cancer progression and that the patterns of these changes are relevant to clinical prognosis. Using different laboratory methods, researchers can measure gains and losses in the copy number of chromosomal regions in tumor cells. Then, using mathematical models to analyze these data, they can predict which chromosomal regions are most likely to harbor important genes for tumor initiation and disease progression. The results of such an analysis may be depicted as a hierarchical treelike branching diagram, referred to as a "tree model of tumor progression".

Researchers use a technique called microarray Comparative Genomic Hybridization (CGH) to look for genomic gains and losses or for a change in the number of copies of a particular gene involved in a disease state. In microarray CGH, large pieces of genomic DNA serve as the target DNA, and each spot of target DNA in the array has a known chromosomal location. The hybridization mixture will contain fluorescently labeled genomic DNA harvested from both normal (control) and diseased (sample) tissue.

Therefore, if the number of copies of a particular target gene has increased, a large amount of sample DNA will hybridize to those spots on the microarray that represent the gene involved in that disease, whereas comparatively small amounts of control DNA will hybridize to those same spots. As a result, those spots containing the disease gene will fluoresce red with greater intensity than they will fluoresce green, indicating that the number of copies of the gene involved in the disease has gone up.

http://www.ncbi.nlm.nih.gov/About/primer/microarrays.html