Haploinsufficiency for Tumor Suppression: The Hazards of Being Single and Living a Long Time

By and large, gene expression levels in diploid organisms reflect the combined transcription of both copies, or alleles, of that gene. Notable exceptions include genes on the X chromosome and imprinted genes. The presence of genes in only one copy or in more than two copies can have major effects on the development and fitness of an organism. Many examples of these gene dosage effects can be found in model genetic organisms such as Drosophila and in inherited disorders in humans. Examples include the well-known effects of trisomy and contiguous gene deletion syndromes. It is now a well-established fact that inheritance of one mutant copy of a tumor suppressor gene (TSG) may predispose an individual to cancer because of loss of the remaining wild-type allele in somatic cells, resulting in cells completely devoid of the TSG product (for a...