Tumorigenic and Developmental Effects of Combined Germ-line Mutations in Rb and p53

During the past 20 years, considerable progress has been made in elucidating the genetic changes that occur in cancer. It is clear that emerging tumor cells acquire mutations in at least two classes of genes: oncogenes and tumor suppressor genes (Vogelstein and Kinzler 1993). Oncogenes are typically activated during tumorigenesis, and, therefore, they are thought to encode positive regulators of cell growth. In contrast, the commonly observed mutations in tumor suppressor genes are inactivating, leading to the suggestion that these genes encode negative regulators of cell growth or in some other way negatively affect tumorigenic progression (Knudson 1993). Due to the presence of two functional alleles of each tumor suppressor gene in most individuals, the complete loss of these functions requires two independent somatic mutational events (Knudson 1993). In addition, inheritance of a mutant allele of seven of the eight known tumor suppressor genes results in a greatly increased tumor...