Positional approaches to cancer genetics.
Robertson-GP; Sargent-L; Nelson-MA
Tumor Supressor Genes, Volume I: Pathways and Isolation Strategies. El-Deiry WS, ed., Totowa, NJ: Humana Press Inc., 2003 Mar; :337-361
Loss of genetic material accumulates during tumor development as cancer cells select for the physical removal or functional inactivation of genes whose encoded proteins regulate normal cellular behavior. The hallmark indication for this type of; gene, now termed a tumor suppressor gene, is a genetic event resulting in loss or deletion of chromosomal material. Position-oriented approaches have taken advantage of the intimate involvement of tumor suppressor gene inactivation through deletion to localize, identify, and demonstrate the involvement of these genes in carcinogenesis. Since deletion of genetic material exceeds genomic amplifications in most cancer types, loss of gene function appears to playa prominent role in tumor formation. However, despite the intimate involvement of tumor suppressor genes in the neoplastic process, relatively few of these genes have been identified, leaving the identity of the majority unknown. Thus, the use of position-based strategies for mapping and isolating tumor suppressor genes remains a prime tool in their identification. In this chapter we discuss the positional approaches used in the localization and identification of tumor suppressor genes. This process can be broadly divided into the following 4 steps leading to the identification and validation of these genes: (a) genome-wide surveys to identify the chromosomal location of genes potentially involved in tumor development; (b) refinement and/or confirmation of the chromosomal region of loss or deletion; (c) cloning genes from consistent regions of loss; and (d) validating the candidate gene as a tumor suppressor through the identification of truncating or missense mutations as well as by growth and tumor suppressing assays.
Genes; Genetics; Tumors; Genetic-engineering; Genetic-disorders; Genetic-factors; Cancer; Tumorigenesis; Chromosome-damage; Chromosome-disorders; Biological-monitoring; Biological-effects; Cell-function; Cell-damage; Cell-biology
Book or book chapter
Tumor Supressor Genes, Volume I: Pathways and Isolation Strategies