Tumor Suppressors

Tumor suppressor genes were first identified by making cell hybrids between tumor and normal cells. On some occasions a chromosome from the normal cell reverted the transformed phenotype. Several familial cancers have been shown to be associated with the loss of function of a tumor suppressor gene. They include the retinoblastoma susceptibility gene (RB), Wilms' tumors (WT1), neurofibromatosis type-1 (NF1), familial adenomatosis polyposis coli (FAP), von Hippel-Lindau syndrome (VHL), and those identified through loss of heterozygosity such as in colorectal carcinomas (called DCC for deleted in colon carcinoma) and P53 which was originally thought to be a proto-oncogene. However, the wild-type P53 protein suppresses the activity of mutant alleles of p53 which are the oncogenic forms of P53.