Identification and validation of tumor suppressor genes.

Cancers are associated with frequent deletions of genetic material that select for the loss of genes regulating normal cellular physiology. Although several cancer suppressor genes have been identified from these areas of deletion, the identities of the vast majority remain unknown, making approaches leading to their localization, identification, and validation an important continuing endeavor. Those currently characterized cancer suppressors include regulators of aspects of the cell cycle, growth and transcriptional regulators, DNA repair enzymes, differentiation factors, cell motility elements, and regulators of signal transduction. Several inherited cancer predisposition genes have been mapped and cloned using meiotic genetic linkage mapping but less success has been achieved identifying those genes involved in nonfamilial cancer. The future localization, identification, and validation of these genes are likely to involve a combination of complementary position-oriented and function-driven approaches, some of which are detailed in this article.