Abstract
Background: The p53 gene is the most frequently mutated gene in cancer and accordingly has been the subject of intensive investigation for almost 30 years. Loss of p53 function due to mutations has been unequivocally demonstrated to promote cancer in both humans and in model systems. As a consequence, there exists an enormous body of information regarding the function of normal p53 in biology and the pathobiological consequences of p53 mutation. It has long been recognised that analysis of p53 has considerable potential as a tool for use in both diagnostic and, to a greater extent, prognostic settings and some significant progress has been made in both of these arenas. Objective: To provide an overview of the biology of p53, particularly in the context of uses of p53 as a diagnostic tool. Methods: A literature review focused upon the methods and uses of p53 analysis in the diagnosis of sporadic cancers, rare genetic disorders and in detection of residual disease. Conclusion: p53 is currently an essential diagnostic for the rare inherited cancer prone syndrome (Li-Fraumeni) and is an important diagnostic in only a limited number of settings in sporadic disease. Research in specific cancers indicates that the uses of increasingly well informed p53 mutational analysis are likely to expand to other cancers.
Acknowledgments
We would like to thank R Polanski of the p53/MDM2 research team for the images used for , C Rubbi for critically reviewing the manuscript and A Pettitt and TM Jones for comments and helpful discussions. Work in our laboratory is funded by Cancer Research UK, the North West Cancer Research Fund and Mersey Kidney Research and we are grateful for their support.