SELECTIVE SENSITIVITY TO RADIATION OF CEREBRAL GLIOBLASTOMAS HARBORING P53 MUTATIONS

Recent studies suggest that a balance may exist between the cell cycle arrest and apoptosis-inducing functions of the p53 tumor suppressor g ene. Adenoviral p21 transduction attenuates apoptosis, whereas deletio n of the p21 gene promotes it, and p21-null xenografts respond better than isogenic p21-wild type tumors to irradiation. Hence, the role of p53 in dictating the clinical response to radiotherapy and chemotherap y may be more complex than previously thought. We have analyzed surviv al and radiation response (regrowth-free period) of 42 patients with g lioblastomas whose p53 status was determined by a sensitive yeast func tional assay. Multivariate analysis revealed that p53 mutation is asso ciated with longer survival (P < 0.02). Among 36 radiation-treated pat ients, the regrowth-free period after treatment was significantly long er for tumors with p53 mutations (P < 0.0001), and p53 mutation was th e sole independent factor predictive of radiotherapeutic response (P < 0.01). Survival time after regrowth was independent of p53 status, su ggesting that the difference in survival was related to the treatment rather than to the intrinsic aggressiveness of the tumor. Thus, in thi s Northern Japanese population, p53 mutation is a marker for better ra diation response in glioblastomas, and this results in significantly l onger survival.