P53 - THE MOST IMPORTANT OR THE MOST OVERESTIMATED TUMOR GENE

Mutations in the tumour-suppressor gene p53 are the most frequent molecular alterations detected in human tumours. p53 protein, which has been called ''guardian of the genome'', seems to play a key role in cellular DNA repair. Loss of p53 protein function by genetic mutation thereby makes the cell vulnurable to DNA damage, and disposes it to malignant transformation. In different human tumour types the prognostic relevance of p53 alterations is quite variable: While there is evidence of poor prognosis in breast cancer carrying p53 alterations, no such prognostic correlation could be found in low grade astrocytic gliomas. In both tumour types p53 mutations are equally frequent. Malignant transformation is considered a multistep process, and p53 mutations occur at different positions in this cascade in different tumour types. While p53 mutations seem to be an early event in astrocytic gliomas, they affect e.g. colon tumours rather late, during malignant progression from adenoma to carcinoma. These observations underscore the biological importance of p53 mutations in human tumour formation, even if the simple investigation for a prognostic relevance may lead to different results in tumours of different tissues.