Implications of the p53 tumor-suppressor gene in clinical oncology.

Abstract

PURPOSE The p53 gene encompasses 16 to 20 kb of DNA on the short arm of human chromosome 17. It encodes for a 393-amino acid nuclear phosphoprotein involved in cell-cycle control. Loss of normal p53 function is associated with cell transformation in vitro and development of neoplasms in vivo. During the past few years, the dramatic progress in the molecular biology of p53 has raised the exciting prospect for cancer management. The purpose of this review is to assess the potential role of p53 in clinical oncology. DESIGN Data on the alterations in the p53 gene in human cancers, with special emphasis on the clinical implications of changes in the p53 gene in the pathogenesis, diagnosis, prognosis, and therapy of human cancers, are summarized in this review. RESULTS AND CONCLUSION Current evidence suggests that abrogation of normal p53 pathway is a common feature in human cancers, and it appears to be a critical step in the pathogenesis and progression of tumors. Analysis of p53 function and mutations in human cancers may lead to identification of the precise nature of the carcinogenic damage in human tissues. These laboratory investigations and biologic findings have raised the possibility to screen patients at increased risk for cancer, aid the diagnosis made by traditional methods, assess the prognosis of individual cancer patient, design treatment protocols, and test the response to therapeutic agents.