BIOLOGICAL AND CLINICAL IMPORTANCE OF THE P53 TUMOR-SUPPRESSOR GENE

The p53 tumor suppressor gene controls cellular growth after DNA damag e through mechanisms involving growth arrest and apoptosis, Mutations that inactivate p53 occur commonly in virtually all human malignancies and can be detected by sequencing of the p53 gene, immunohistochemica l staining of tumor tissue with anti-p53 antibodies, single-strand con formation polymorphisms, or other biological assays. Identification of p53 mutation in the germ line is diagnostic of the cancer-prone Li-Fr aumeni syndrome, Alterations of the p53 gene result in defective cellu lar responses after DNA damage and predispose cells to dysregulated gr owth, tumor formation and progression, and potential resistance (of tu mor cells) to certain chemotherapeutic agents or ionizing radiation, A variety of tumors involving mutant p53 have a worse prognosis than tu mors of the same type containing no p53 mutations. New diagnostic and therapeutic strategies are evolving as the p53 pathways of cell-cycle arrest and apoptosis become elucidated.