A deadly inheritance

Abstract

THE p53 gene has led a short experimental life, but one filled with intrigue and irony. The latest twist is reported in two papers, one in Science1 and one that appears on page 747 of this issue'. Both show that inherited mutations in p53 result in a predisposition to cancer. Twelve years ago, p53 protein was discovered through its association with the oncogene products of DNA tumour viruses1'. The gene encoding the protein was initially believed to be an oncogene because p53 clones, including one obtained from normal mouse liver, could transform recipient cells"'. But several unexpected observations led to doubts about the precise role of p53 in neoplasia. For example, it was shown that the p53 clone from normal mouse liver had sustained a mutation during the cloning process; normal (wild-type) p53 genes actually have no transforming ability. Furthermore, rearrangements and deletions of p53 were observed in.